curs-5-mai 2015 - ficat si pancreas -final de prezentat-recovered]

7/23/2019 Curs-5-Mai 2015 - Ficat Si Pancreas -Final de Prezentat-recovered]

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Universitatea Titu Maiorescu

C U R S M E D I C I N A I N

T E R N A

G A S T R O E N T E R O L O G I E ( I V )

P r o f u n i v d r I o n C . T i n t o

Motion and Activity

• The position of the liver in the body is notThe position of the liver in the body is not

static.static.

– moves up and down with the diaphragm andmoves up and down with the diaphragm androtates during respiration.rotates during respiration.

– rotates backward when an individual lies down inrotates backward when an individual lies down in

the supine position.the supine position.

• The upper surface of the liver can move upward fromThe upper surface of the liver can move upward from1 cm to 10 cm when full expiration follows deep1 cm to 10 cm when full expiration follows deep

inspiration.inspiration.

The Anatomy of the Liver

!"#$ %istology

• lobules >> roughlyhexagonal structuresconsisting of hepatocytes. Radiate

outward from a centralvein.• At each of the sixcorners of a lobule is aportal triad

( p.arteriole,p.venule &bile duct)•etween thehepatocytes are theliver sinusoids.

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&igure '(.'0 iver %istology

)ormal iver * Microscopy

iver &unctions+

• Metabolism , -arbohydrate &at /rotein

• Secretory , bile ile acids salts /

pigments• Excretory , ilirubin drugs toxins

• Synthesis , Albumin coagulation

factors• Storage , "itamins carbohydrates etc.

• Detoxification , toxins ammonia etc.

Hepatic Physiology

• Liver• Largest solid organ in the body

• erforms over !"" chemical processes

• roduces over #$" different proteins

• Makes clotting factors for the blood

• 2tores / releases s%gar as glycogen• Metaboli3es detoxifies& synthesi'es

-hronic iver

4isease

4-Synthesis:- Albumin- Coagulation facto

'e$ti P*+,io-o+ 1- homeostasis; glycogenolysis &

gluconeogenesis

1-Storage:- Glycogen- Iron- Cu, Iron, vitamins-!Met$&o-i,/ 0 C$r&o*+dr$te% F$t 1 Protein

2Deto3ifi$tion 0

to3in,% $//oni$% et

Catabolism of hormonesan other serum !roteins

4Seretor+

0 &i-e% 5i-e $id,% ,$-t, 1 i/ent,

"ile e#cretion

T*ere $re ei*t -iver ,e/ent,.

Se/ent " i, ,o/eti/e, divided into ,e/ent "$ $nd "& $ordin to 5i,/ut*.

T*e nu/&erin of t*e ,e/ent, i, in $ -o67i,e /$nner (fiure).

Se/ent 8 ($ud$te -o&e) i, -o$ted o,terior-+. It i, not vi,i&-e on $ front$-vie7.

#(S)*THET+, -*,T+/*S

• production and release of circulating factors critical to thecoag%lation cascade

• the single most sensitive tests of liver function are measures ofcoagulation f%nction0+nternational *ormali'ed 1atio 2+*13 and

factor "!! and factor " levels.

• synthesi'es a 4ide variety of plasma proteins& the mostimportant of 4hich is alb%min.

• variety of acute*phase proteins and cytokines that have importantinteractions with a variety of inflammatory& infectio%s& andreg%latory processes.

5(Metabolism

• ,arbohydrate Metabolism – critical storage site of glycogen and is essential to the maintenance of

systemic gl%cose homeostasis thro%gh a complex process involving broadinteractions 4ith lipid metabolism.

– The liver also metaboli'es lactate& and the ,ori cycle is important inmaintaining peripheral gl%cose availability in the setting of anaerobicmetabolism.

•Lipid Metabolism – mod%lator of lipid metabolism& critical role in the synthesis of lipoproteins&

triglycerides& gl%coneogenesis from fatty acids& and cholesterol metabolism. – cholesterol is synthesi'ed in the liver and is %sed most importantly for bile

salt synthesis.

• 6ilir%bin Metabolism – 6ilir%bin circ%lates bo%nd to alb%min in the blood. – +t is actively ta7en %p by hepatocytes& 4here it is gl%c%ronidated and actively

secreted into bile. – 6enign disorders of bilir%bin metabolism incl%de

• con8%gated 2direct3 hyperbilir%binemia.• D%bin(9ohnson and 1otor:s syndrome& 4hich prod%ce con8%gated 2direct3

hyperbilir%binemia.• ncon8%gated hyperbilir%binemia is seen in ,rigler(*a88ar type ++ and ;ilbert:s

<(6ile and the Enterohepatic

,irc%lation• 6ile is a mixed micelle composed of bile• #( acids and pigments& 5(phospholipids and cholesterol& <(proteins& and

electrolytes.

• The vol%me of bile secreted in an ad%lt ranges from !"" to #""" mL=5> h.

Electrolyte composition of bile is similar to plasma intravenous volumereplacement of a high*volume biliary fistula output can be made milliliter formilliliter with lactated $inger5s solution.

• 1ole of the distal ile%m in the reabsorption of bile salts became clear whenpatients undergoing resection of the ileum for -rohn5s ileitis developedmalabsorption and steatorrhea.

• !t was also noted that such patients had lo4er ser%m cholesterol levels&%ltimately fo%nd to be a res%lt of increased hepatic metabolism ofcholesterol to bile acids to replace the bile acids not absorbed and recirculated.

Traditional &T6s 7iver &unctional Test8

Traditional L-T?s 2Liver -%nctional

Test8• ALT+ alanine aminotransferase 729T8

• AST+ aspartate aminotransferase 729:T8

• Al7aline Phosphatase @ 6ilir%bin

Traditional L-T?s

• ALT ;PT

• &ound primarily in hepatocytes

• 1eleased 4hen cells are h%rt or destroyed• )ormal levels depend on the reference range which

actually differs lab to lab

• ,onsidered normal bet4een !(>" =L

• robably should be half of this 7;*'0<8

Traditional L-T?s

• AST;/T

• &ound in many sources including liver heart

muscle intestine pancreas

• *ot very specific for liver disease

• :ften follows AT to a degree

• #levated ' or =+1 7vs. AT8 in alcoholics

• )ormal range+ >*'0 U?

Traditional L-T?s

• Al7aline Phosphatase

• &ound in liver 7especially biliary tract8 bones

intestines / placenta

• @&ractionated or @isoen3ymes to source

• Liver AP rises 4ith obstr%ction or infiltrative

diseases 2i.e.& stones or t%mors3

• )ormal range+ '0*B0 U?

Traditional L-T?s

• 6ilir%bin+ two primary sources

• +ndirect 2%ncon8%gated8+ old red cells removed by the

spleen sent to the liver

• Direct 2or con8%gated8 iver @adds gl%c%ronic acid& making these cells water soluble for excretionC nowcalled direct 7or conDugated8

)ormal range+ less than 0.> mg?4l

• Total bilir%bin incl%des both direct and indirect types

Patterns of Abnormal

• Elevations in ALT @ AST only s%ggests cell%lar

in8%ry

• #levations in Alk hos / ilirubin+ suggests

cholestasis or obstr%ction

• Mixed pattern+ AT A2T A / ili+ probably the mostcommon scenario

LIVER DISEASE

Vir$- 'e$titide,

"iral %epatitides

• Hepatitis A& 6& ,& D& E& ;

• ,ytomeglovir%s 2,M3

• Herpes ir%s 2HS3

C*roni 'e$titi,

,hronic HepatitisOverview

• Progression to cirrhosis over 5" years5

– #BC to 5$C in liver clinic series

– #C to #"C in comm%nity cohort series

• eading cause of chronic liver disease cirrhosis %-- and

liver transplantation 7∼(0E8(

-4 Aetiology-4 Aetiology

S%rgical Sieve

F iral

F A%toimm%ne ( A%toimm%ne hepatitis& P6,& PS,

F ;enetic ( ilson?s& Haemochromatosis& Alpha #antitrypsin deficiency

F Toxic = Dr%gs alcoholic& paracetamol

F *on(alcoholic fatty liver 2DM = metabolic syndrome&

pregnancy& idiopathic3

4ifferential 4iagnoses4ifferential 4iagnoses

F 1*7Decompensated3 Alcoholic liver disease

F 5(iral liver disease

F <(A%toimm%ne liver disease& ilson?s& HH etc

F >(Hepatocell%lar ,arcinoma

F !(Pancreatic ,ancer

F $(,ryptogenic Liver ,irrhosis

hat f%rther history 4o%ld be neededF

hat signs 4o%ld yo% loo7 for on examinationF

%ow would you investigate this%ow would you investigate this

patient<patient<6edside

F /bservations& 6M& fl%id balance& 4eight

6lood tests

F L-Ts 2pre=post3 2incl%ding alb%min3& +*1

F -6,& @Es& ,1P

F Liver screen a%toantibodies& alpha(# antitrypsin&

caer%loplasmin& ser%m copper& ferritin& viral hepatitis

serology

+maging

F S abdomen G portal vein doppler

F ,1& ,T& M1+& M1,P

Special tests

F Ascitic tap& /;D 2oesophageal varices3& liver biopsy

,hronic H, +nfectionNatural History

Expos%re2Ac%te Phase3

1esolved ,hronic

,irrhosisStable

Liver DecompensationHepatocell%lar ,arcinoma

!C(5!C over 5"(<" years

#!(>!C!!(B!C

!C=yr decompensation

5(BC=yr H,,

I!(J!C

oynard T. ancet. 1GGB =(G+>';*>='.

Mathurin . %epatology. 1GG> 'B+>H>*>B'.

enhamou I. %epatology. 1GGG =0+10;(.

Primary Point

of +ntervention

Treatment

;oals iral eradication

Prevention ofdisease progression

Su,t$ined -o,, of'CV RNA in ,eru/

(49 /o, o,tT3)

Nor/$-i:$tion of-iver en:+/e,

I/roved -iver*i,to-o+

I/roved ;u$-it+ of-ife

Tre$t/ent

Endoint,

Jhat is your management plan<Jhat is your management plan<

,onservative

F Alcohol abstinence& optimise n%trition& lo4 salt diet& fl%id

restriction

Medical

F itamin 6 s%pplementation 2+=P/3& chlordia'epoxideF Di%retics

F Paracentesis 2give alb%min3

F *; feeding

F Antibiotics 2F S6P3

F Steroids G alb%min 2*.6. avoid *a,l3

F Lact%lose 2in hepatic encephalopathy3

S%rgical

F Liver transplantation

1ecommended Treatment 5""B

,hronic Hepatitis ,

Peginterferon G 1ibavirin Therapy

AASLD Practice ;%idelines

Dr%g doses

PE;(+-* (5b 2Peg(+ntron K

3 #.!µ

g=7g 4ee7ly Gribavirin B"" mg 2;5=<3&#"""(#5"" mg 2;#3 daily

PE;(+-* (5a 2Pegasys K 3 #B" µg 4ee7ly Gribavirin B"" mg 2;5=<3&#"""(#5"" mg 2;#3 daily

Treatment d%ration &or genotype 1 (> weeks superior to '( weeks

&or genotypes '?= (> weeks K '( weeks

Strader DB, et al. Hepatology. 2004;39:1147-1171.

Autoi//une 'e$titi,Autoi//une 'e$titi,

hat is a%toimm%ne hepatitisF

• A%toimm%ne hepatitis is a disease in which thebody6s own immune system attacks the liver andcauses it to become inflamed. The disease ischronic& meaning it lasts many years. +f%ntreated& it can lead to cirrhosis and liver

fail%re.

Autoimmune %epatitis Autoimmune %epatitis

F A%toantibodies against hepatocytes

F )o%ng=middle age& mainly 4omen

F Presentation 8a%ndice& 1 pain& systemic symptoms

F May be associated 4ith other a%toimm%ne conditions

F +nvestigations

- Type 1 anti(smooth m%scle antibodies 2B"C3& anti(n%clear

antibodies 2#"C3

- Type 2 2children3 anti(liver=7idney microsomal type #

antibodies

( Liver biopsy

F 1x imm%nos%ppressant:s 2steroids& a'athioprine3&

transplant

Ho4 is a%toimm%ne hepatitis

diagnosedF• Autoimmune hepatitis often occurs suddenly. !nitially you may feel like

you have a mild case of the flu. As # does not often offer the examinermuch information to confirm a diagnosis of autoimmune hepatitis yourdoctor will need to useLblood tests and a liver biopsy

– antin%clear antibody 2A*A3& – smooth m%scle antibody 2SMA3& – Liver=7idney microsomal antibody 2LM(#3 – and anti(mitochondrial antibody 2AMA3

• are all of use as is finding an increased +mm%noglob%lin ; level.

• %owever the diagnosis of a%toimm%ne hepatitis al4aysreN%ires a liver biopsy.

• !n complex cases a scoring system can be used to help determine if a

patient has autoimmune hepatitis which combines clinical and laboratory

hat ca%ses a%toimm%ne

hepatitisF

• )o%r imm%ne system normally attac7s bacteria&vir%ses and other invading organisms. +t is nots%pposed to attac7 yo%r o4n cellsO if it does& the

response is called a%toimm%nity.

• +n a%toimm%ne hepatitis& yo%r imm%ne systemattac7s yo%r liver cells& ca%sing long(terminflammation and liver damage.

• Scientists don?t 7no4 4hy the body attac7s itself inthis 4ay& altho%gh heredity and prior infections mayplay a role.

hat are the symptoms and

complications of a%toimm%ne

hepatitisF:ften the symptoms of autoimmune hepatitis are minor.

Jhen symptoms do occur the most common are

fatig%e

abdominal discomfort

aching 8oints

8a%ndiceenlarged liver

na%sea

Liver biopsy histology at initial presentation showing peri*portallymphocytic infiltration and extensive peri*portal fibrosis.

Ho4 is a%toimm%ne hepatitis

treatedF

• The goal of treatment is to stop the body?s attac7 on itself bys%ppressing the imm%ne system. – prednisone&& – a'athioprine 2+m%ran3

• Treatment starts 4ith a high dose of prednisone. hensymptoms improve& the dosage is lo4ered and a'athioprinemay be added.+n most cases& a%toimm%ne hepatitis can becontrolled b%t not c%red. That is 4hy most patients 4ill needto stay on the medicine for years& and sometimes for life.

• long*term use of steroid can ca%se serio%s side effectsincl%ding diabetes& osteoporosis& high blood press%re&gla%coma& 4eight gain and decreased resistance to infection.

-onventional Treatment

$egimens

Pri/$r+ 5i-i$r+ Cirr*o,i

Pri/$r+ S-ero,in C*o-$niti,

- and 2-- and 2-

Primary 6iliary ,irrhosis

F ,hronic gran%lomato%s inflammation of interlob%lar bile

F A%toimm%ne anti(mitochrondrial antibody 2JBC3

F Associated 4ith other a%toimm%ne conditions

F -M J#& !" y=o

Primary Sclerosing ,holangitis

F +nflammation& fibrosis and strict%res 2beading?3

of intra and extra(hepatic bile d%cts

F F A%toimm%ne A*,A 2B"C3

F Associated 4ith +6D

F 5"(<"C develop cholangiocarcinoma

Jilson6s / 1AT 4eficiencyJilson6s / 1AT 4eficiency

ilson?s Disease

• A1 defect in copper transporting ATPase

• ,opper acc%m%lates in liver G ,*S G

ayser(-leischer rings• 1x penicillamine& transplant

Alpha(# Antitrypsin Deficiency

• A1 deficiency of Q#AT• Serine protease inhibitor prod%ced by liver

• Emphysema G liver damage G H,,

%ereditory %aemochromatosis%ereditory %aemochromatosis

F Defect in H-E ca%ses increased

intestinal iron absorption

F +ron acc%m%lates in liver& 8oints

2arthralgia3& pancreas 2bron'e

diabetes3& heart 2dilated

cardiomyopathy3& pit%itary

2hypogonadism3& adrenals& s7in

F +x L-Ts& ser%m ferritin& iron&

transferrin sat%ration& T+6,& H-E

genotyping& gl%cose& x(ray 8oints&

liver biopsy 2Perl?s stain3& M1+ liver&

E,;& Echo

F 1x venesection& lo4 iron diet& treat

diabetes& heart fail%re etc. ;enetic

screen relatives.

%i t th l - it l

%istopathology -ongenital

hemocromatosis

CIRROSIS OF T'E LIVER

Description

• A chronic progressive disease of the liver

– #xtensive parenchymal celldegeneration

– Destr%ction of parenchymal

4efinition * -irrhosis

End stage of chronic

hepatitis conversion of normal

architect%re toabnormal nod%les

nod%lar regeneration

fibrosis

-irrhotic iver

Liver cirrhosis

Description

• 1egenerative process is

disorgani'ed

• resulting in abnormal blood vessel

and bile duct relationships fromfibrosis

Description

• *ormal lob%lar str%ct%re distorted byfibrotic connective tiss%e

• Lob%les are irreg%lar in si'e andshape 4ith impaired vasc%lar flo4

• +nsidio%s& prolonged co%rse

Etiology and Pathophysiology

• ,ell necrosis occ%rs

• Destroyed liver cells arereplaced by scar tiss%e

• *ormal architect%re becomes

nod%lar

• -o%r types of cirrhosis

– #(Alcoholic 2Laennec?s3 cirrhosis

– 5(Postnecrotic cirrhosis

– <(6iliary cirrhosis

– >(,ardiac cirrhosis

• #(Alcoholic 2Laennec?s3

,irrhosis

– Associated with alcohol abuse

– receded by a theoretically

reversible fatty infiltration of the liver

– Jidespread scar formation

• 5(Postnecrotic ,irrhosis

– ,omplication of toxic or viral hepatitis

– Acco%nts for 5"C of the cases of

cirrhosis

– 6road bands of scar tiss%e form

4ithin the liver

#tiology and athophysiology

• <(6iliary ,irrhosis

– Associated 4ith chronic biliary

obstr%ction and infection

– Acco%nts for #!C of all cases ofcirrhosis

• >(,ardiac ,irrhosis

– 1es%lts from longstanding severe

right(sided heart fail%re

%istopathology

Morphologic -lassification

• 1*Micronodular cirrhosis – *od%les less than < mm in diameter

– 6elieved to be ca%sed by alcohol&hemochromatosis& cholestatic ca%ses

of cirrhosis& and hepatic veno%s o%tflo4

obstr%ction

– 5(Macronod%lar cirrhosis

Diagnostic St%dies

• Liver f%nction tests

• Liver biopsy• Liver scan

• Liver %ltraso%nd

Which method: blood sample or

pliver stifness?

• %epascore

• &ibrotest

• &ibrometer

Liver stiffness

2-ibroScan3

Li tif

Liver stifness

Stiness

'ortal (brosis

Cholestasis

'ortal bloo)o*

In)ammation

Steatosis+

Centrolobular(brosis

Sinusoial(brosis

Si f CSi f C

Signs of CSigns of C

Manifestations of Liver ,irrhosis

-linical Manifestations

Early Manifestations• Abdominal pain

• -ever • Lassit%de 2la'iness3

• eight loss

• Enlarged liver or spleen

,linical Manifestations

Late Manifestations

• T4o ca%sative mechanisms

– Hepatocell%lar fail%re

– Portal hypertension

9a%ndice

• +ntermittent 8a%ndice is characteristic

of biliary cirrhosis• Late stages of cirrhosis the patient

4ill %s%ally be 8a%ndiced

Iaundice or 2cleral !cterus

9a%ndice

• /cc%rs beca%se of ins%fficient

con8%gation of bilir%bin by the livercells& and local obstr%ction of biliary

d%cts by scarring and regenerating

tiss%e

• Spider angiomas 2telangiectasia&

spider nevi3

• Palmar erythema

Endocrine Dist%rbances

• Steroid hormones of the adrenalcortex 2aldosterone3& testes& and

ovaries are metaboli'ed and

inactivated by the normal liver

Endocrine Dist%rbances

• Alteration in hair distrib%tion

– Decreased amo%nt of p%bic hair – Axillary and pectoral alopecia

Hematologic Disorders

• 6leeding tendencies as a res%lt

of decreased prod%ction of

hepatic clotting factors 2++& ++& +&

Hematologic Disorders

• Anemia& le%7openia& andthrombocytopenia are believed

to be res%lt of hypersplenism

Peripheral *e%ropathy

• Dietary deficiencies of thiamine& folicacid& and vitamin 6#5

2pider Angiomata

2pider )evi

)ail -lubbing

4upuytren5s -ontracture

Ascites

• The most successful therapeutic regimenis the combination of single morning oraldoses of 2pironolactone and &urosemidebeginning with 100 mg and (0 mg

• Two maDor concerns with diuretic therapyfor cirrhotic ascites+

– :verly rapid removal of fluid – rogressive electrolyte imbalance

Co/-i$tion,

Ma8or ,omplications of ,irrhosis

<$undie

Portal hypertension

ariceal bleedingAscites

Spontaneo%s bacterial peritonitis

Hepatorenal syndrome

Hepatic encephalopathy

-!$$:2!2 :& T%# !"#$

-omplications

• 1*ortal hypertension and esophageal varices

• '*eripheral edema and ascites

• =*%epatic encephalopathy

• (*%epatorenal syndrome

'e$toren$- ,+ndro/e

%epatorenal syndrome

• ac%te renal fail%re coupled with advanced

hepatic disease 7due to cirrhosis or less often

metastatic tumor or severe alcoholic hepatitis8

• characteri3ed by+

– :liguria

– benign urine sediment

– very lo4 rate of sodi%m excretion – progressive rise in the plasma creatinine

concentration

%epatorenal 2yndrome

• 1ed%ction in ;-1 often clinically

mas7ed

• Prognosis is poor %nless hepaticf%nction improves

• *ephrotoxic agents and

overdi%resis can precipitate H1S

%epatopulmonary syndrome

• Hepatop%lmonary syndrome

– Liver disease

– +ncreased alveolar(arterial gradient 4hile

breathing room air

– Evidence for intrap%lmonary vasc%lar

abnormalities& referred to as intrap%lmonary

vasc%lar dilatations 2+PDs3

%epatic %ydrothorax

• leural effusion in a patient with cirrhosis and

no evidence of underlying cardiopulmonary

disease

• Movement of ascitic fluid into the pleural

space through defects in the diaphragm and

is usually right*sided

• 4iagnosis *pleural fluid analysis – reveals a transudative fluid

– serum to fluid albumin gradient greater than 1.1

%epatic hydrothorax

• -onfirmatory study+

– 2cintigraphic studies demonstrate tracer in the chest cavity

after inDection into the peritoneal cavity

• Treatment options+ – diuretic therapy

– periodic thoracentesis

– T!2

ortopulmonary %T)

• $efers to the presence of p%lmonary hypertensionin the coexistent portal hypertension

• revalence in cirrhotic patients is approximately '

percent• 4iagnosis+

– 2uggested by echocardiography

– -onfirmed by right heart catheteri3ation

%epatic #ncephalopathy

• 2pectrum of potentially reversible neuropsychiatric

abnormalities seen in patients with liver dysfunction

– 4iurnal sleep pattern pertubation

– Asterixis – %yperactive deep tendon reflexes

– Transient decerebrate posturing

-omplications

Peripheral Edema and Ascites

F Ascites+

** !ntraperitoneal accumulation ofwatery fluid containing small

amounts of protein

#arly Manifestations

• :nset usually insidious

• 9! disturbances+

– Anorexia

– 4yspepsia

– &latulence

– )*" change in bowel habits

-omplications

Portal Hypertension

• Primary mechanism is the increased resistance

to blood flo4 thro%gh the liver

Portal Hypertension

Esophagea

arices

med%sae

2dilated abd.

veins3

Hemorrhoids

Arterioveno%ssh%nting

Hypersplenism

Moderate anemia

*e%tropenia

Thrombocytopeni

Mar7ed ascites

-omplications

Portal Hypertension

• ,haracteri'ed by

– +ncreased veno%s press%re inportal circ%lation

– Splenomegaly

– Esophageal varices – Systemic hypertension

Portal Hypertension

• *ormal press%re ranges from I to #" mm Hg.

• +n portal hypertension& press%re exceeds #" mm Hg& averagingaro%nd 5" mm Hg and occasionally rising as high as !"$"mm Hg.

• +n extrahepatic portal vein thrombosis 24itho%t liver disease3&collaterals in the diaphragm and in the hepatocolic&hepatod%odenal& and gastrohepatic ligaments transport bloodinto the liver aro%nd the occl%ded vein 2hepatopetal3.

• +n cirrhosis& collateral vessels circ%mvent the liver and deliverportal blood directly into the systemic circ%lation2hepatof%gal3O these collaterals give rise to esophageal andgastric varices.

Portal Hypertension

• +solated thrombosis of the splenic vein ca%seslocali3ed splenic venous hypertension and gives rise to

large collaterals from spleen to gastric fundus.• &rom there the blood returns to the main portal system

through the coronary vein.• !n this condition gastric varices are often present without

esophageal varices.

• spontaneo%s bleeding is relatively uncommon exceptfrom those at the gastroesophageal DunctionC spontaneousbleeding from gastric varices can sometimes occur.

• -ompared with adDacent areas of the esophagus andstomach the gastroesophageal Dunction is especially richin submucosal veins which expand disproportionately in

patients with portal hypertension.• The ca%se of variceal bleeding is most probably

r%pt%re d%e to s%dden increases in hydrostaticpress%re.

-omplications

Portal Hypertension

Splenomegaly

• ack pressure caused by portal hypertension → chronic

passive congestion as a result of increased pressure inthe splenic vein

-omplications Portal Hypertension

Portal Hypertension

Esophageal Varices

F !ncreased blood flow through the

portal system results in dilationand enlargement of the plexus

veins of the esophagus and

produces varices

-ollaborative -are

Esophageal Varices

• Endoscopic sclerotherapy or ligation

• 6alloon tamponade• S%rgical sh%nting proced%res 2e.g.& portacaval

sh%nt& T+PS3

Treatment of esophageal varices

Treatment of esophageal varicesActive bleeding• ,entral line @ p%lmonary artery press%res• 6lood transf%sions @ fresh fro'en plasma for

clotting factors• Somatostatin or asopressin constrict g%t vessels• *itroglycerin( to co%nter negative affects of

vasopressin• Air4ay=trach

Later prevention of re(bleeding• 6eta(bloc7ers• Long(acting nitrates• Soft food& che4 4ell& avoid intra(abdominal press%re• Protonix 2pantopra'ole3

R id E d =

R$id Endo,o+=

Sclerotherapy

• A sclerosantsolution.ethanolamine oleateor soium tetraecylsul!hate/ is in0ecteinto the bleeingvari# or the overlyingsubmucosa

• Com!lications can

inclue fever,ys!hagia an chest!ain, ulceration,

stricture, an .rarely/

6and ligation

• "an ligation isachieve by a

baning eviceattache to the ti!of the enosco!e

5$--oon Tu&e T$/on$de>

-omplications

ortal %ypertension

Internal Hemorrhoids

F :ccurs because of the dilation of the

mesenteric veins and rectal veins

-omplications

ortal %ypertension

Caput Medusae

F ,ollateral circ%lation involvesthe s%perficial veins of the

abdominal 4all leading to the

development of dilated veinsaro%nd the %mbilic%s

-omplications

Peripheral Edema and Ascites

F Ascites+

** !ntraperitoneal accumulation ofwatery fluid containing small

amo%nts of protein

-omplications

Peripheral Edema and AscitesF &actors involved in the pathogenesis of ascites+

* %ypoalbuminemia

−↑ evels of aldosterone

−↑ ortal hypertension

4rug Therapy

• There is no specific dr%g

therapy for cirrhosis• Dr%gs are %sed to treat

symptoms and complications ofadvanced liver disease

-ollaborative -are

Ascites

• High carbohydrate& lo4

protein& lo4 *aG diet

• Di%retics

• Paracentesis

aracentesis

• To treat respiratory distress

• Pt 4ill loose #"(<" grams of

protein

• Pt in sitting position• Empty bladder first

• Post((4atch for

hypotension& bleeding&

shoc7 @ infection

eritoneovenous 2hunt

ortosystemic 2hunts

-omplications

Hepatic Encephalopathy

• Liver damage ca%ses blood toenter systemic circ%lation

4itho%t liver detoxification

-omplications

• Main pathogenic toxin is *H<

altho%gh other etiological factorshave been identified

• -reN%ently a terminal complication

-ollaborative -are

• ;oal red%ce *H< formation

– Protein restriction 2"(>"g=day3

– Sterili'ation of ;+ tract 4ith antibiotics 2e.g.& neomycin3

– lact%lose 2,eph%lac3 traps *H< in g%t

– levodopa

Choletat!" Liver Disease

rimary iliary -irrhosis

• 4ifferential diagnosis – 2arcoidosis

– 9ranulamatous hepatitis

– %epatitis -

– 4rug induced hepatitis

– 2-

– Alcoholic liver disease

– !diopathic adult onset ductopenia – Autoimmune hepatitis

&eatures of -

• -linical &eatures• 2icca syndrome ;0E

• Thyroid disease 1;E

• Arthritis 10E

• ess -ommon N;E

– $aynaud6s

– reast cancer

– 2cleroderma – $enal stones

• aboratoryfeatures

• AMA positive 2J!C3

/1• A*A positive

• ASMA positive

•Elevated cholesterol

• Elevated +gM level

'i,to-oi St$in of P5C

-holangio-arcinoma+

Liver biopsy in a patient 4ith a large& right lobe hepatic mass. /nly a small area of the

slide contains hepatocytes. The remainder of the biopsy reveals an infiltrating

neoplasm typical of cholangiocarcinoma. The abnormal

adenocarcinoma(li7e proliferation of t%bo(d%ct%lar str%ct%res& largely seen in the

%pper left hand corner of the photograph& may be impossible to differentiate from

metastatic adenocarcinoma.

I/$e ourte,+ Dr. C*ri, P$$,

-holangio-arcinoma+

#pidemiology• Malignant bile duct cancer arising from

epithelial cells of the intra?extrahepatic bileducts

• $areLbut lethal

• =E of all 9! malignancies

• !ncreases with age 7;0*B0 years old8

Molecular athogenesis

• Malignant transformation incompletely

%nderstood

• Molecular defects involving oncogenes and tumor

suppressor genes• B0*>0E overexpress p;=

• Mutations in oncogenes O*ras c*myc c*neu c*er*'

• :verexpression of M#T hepatocyte growth factor

common feature• 2hare molecular features of hepatocellular carcinoma

Treatment

Surgical

!ntrahepatic cholangiocarcinoma

• %epatic resection

– H1 patients+ H0E = year survival

– =0 patients+ >H?H=?''E survivalerihilar cholangiocarcinoma+

• '0*(0E potentially resectable

• Aggressive resection of bile duct liver resection and

caudate lobectomy

Primary Sclerosing ,holangitis

.Primary Sclerosing ,holangitis 2PS,3

• Associated 4ith %lcerative colitis 2,3• +ncidence of colitis J"C

• <"C of ,, diagnosed in , and PS,

• Ann%al incidence #.!=year

• Lifetime ris7 of #"(#!C

• A%topsy st%dies <"C ,,

• More diffic%lt to diagnose in PS,

• #=< cases of ,, made 4ithin 5 years ofdiagnosis

P i S l i ,h l iti 2PS,3

Primary Sclerosing ,holangitis 2PS,3

• 2mokers and former smokers had

higher rates of cancer

• Alcohol consumption

• $ole of -#A -A*1G*G -A*;0 and

-A*'(' of limited value

$isk &actors

• arasitic infections

• %epatolithiasis

• Toxic exposures+ Thorotrast 7'0*=0years8 auto?rubber?wood*finishing

•i*&raumeni syndrome

• iliary apillomatosis

5uddC*i$ri ,+ndro/e

Mechanism %epatic vein outflow obstruction+

hepatic vein thrombosis 7udd*-hiari syndrome8

p 7 y 8

o /riginal description fatal ac%te thrombosiso Expanded definition ac%te& s%bac%te& or chronic

occl%sions of hepatic vein

o Signs=symptoms hepatomegaly& pain& ascites

o ,a%ses 2most freN%ent to less freN%ent3o Polycythemia vera 2myeloproliferative diseases3

o Pregnancy or post(part%m state

o /ral contraceptives

o Paroxysmal noct%rnal hemoglobin%riao ,ancers& especially hepatocell%lar carcinoma

o +diopathic 2#"C& pres%mably %ndiagnosedthrombogenic disorder3

udd*-hiari syndrome+ pathology

Severe entri-o&u-$r one,tion 1 nero,i,? deree of

nero,i, deend, on deree of *e$ti outf-o7 o-u,ion

udd*-hiari syndrome+ treatment

o Address %nderlying ca%seO high mortality4itho%t treatment

o Ac%te interventionso S%rgical creation of portal(systemic sh%nt 2portal vein to

systemic circ%lation3& 4hich allo4s reverse flo4 thro%ghportal vein& b%t hepatic artery inflo4 preserved to preventinfarction

o Angiographic thrombectomy and=or dilation of hepatic vein

LIVER TUMORS

5enin -iver tu/or,

asic workup

• Differentiate bet4een primary hepatic malignancy

vs. metastatic disease vs. benign

%epatic abscess

• yogenic

• Amebic

• &ungal

• #chinococcal

yogenic abscess

• >0E of liver abscesses are pyogenic

• !ncidence is >*'' per 100000

• -holangitis is the most common cause of liver

abscesses• atient usually present with variable constitutional

symptoms

• U2 -T and M$! are all sensitive modalities for

identifying an abscess however they do notdifferentiate between pyogenic and amebic

yogenic abscess

9ram*negative Aerobes

9ram*positive Aerobes

Anaerobes

-ommon 7P10E8

Escherichia coli Staphylococcusaureus

Bacteroides spp.

Klebsiella

Enterococcus spp.

"iridansstreptococci

Uncommon 71E,

seudomonasProteus

Q*hemolytic

streptococci

Fusobacterium

Enterobacter

Anaerobic

streptococciCitrobacter Clostridium

Serratia actobacilli

T$&-e 8 P+oeni Liver A&,e,, Miro&io-o+

yogenic abscess

• Treated with antibiotics and percutaneous drainage

• :pen surgical drainage is reserved for patients with

concurrent gastrointestinal disease processes that

reRuire surgery or those patients who have failedpercutaneous drainage.

yogenic abscess

yoge c abscess

• Almost uniformly fatal if left untreated.

• Mortality rates 10*'0E

• %igher success rates with antibiotics and drainage vs.

antibiotics and simple aspiration

yogenic abscess

&ungal abscess

• &ungal liver abscesses are being recogni3ed with

increased freRuency and currently account for

approximately 10E of hepatic abscesses

• Candida albicans and other Candida species arefound in approximately >0E of cases

• &ungal liver abscesses are usually multiple and

usually occur in immunocompromised patients.

&ungal abscess

• &ungal liver abscesses are treated with systemicantifungal therapy and drainage of the abscess cavityor cavities by simple aspiration percutaneousdrainage or open surgical drainage

• Amphotericin is the first*line drug of choice forsystemic antifungal therapy because of its broadfungal efficacy

• oricona'ole or ,aspof%ngin may be used to treat

patients who are not responding to Amphotericin orwho have aggressive infections caused by otherfungal species

#chinococcal disease

• Echinococcus is a flat tapeworm

• %uman infestation occurs with consumption of

contaminated vegetables or through contact with

infected animals or soil• E! granulosus forms cysts that are constituted by an

external acellular layer and an inner cellular germinal

layer that produces the brood capsules containing

protoscolicies hydatid sand or daughter cysts

• The outer acellular layer is usually ' to ; mm thickand is composed of fibroblasts that produce acapsule of fibrous connective tissue called the pericyst . The pericyst is calcified in approximately half

of patients.• The symptoms associated with hepatic E! granulosus

can vary considerably

• specific en3yme*linked immunosorbent assay

7#!2A8 and hydatid antigen immunobinding assaysyield a sensitivity and specificity up to G;E and G0Erespectively

• ,hemotherapy 4ith ben'imida'ole compo%nds

7mebenda3ole and albenda3ole8 is the medical

treatment of choice

• More recently pra3iRuantel a synthetic isoRuinoline*pyra3ine derivative has been used in combination

with albenda3ole

• with medical treatment alone only "#$ o% patients

can e&pect clinical and radiographic resolution.

Medical treatment therefore should be used primarily

in conDunction with percutaneous drainage or surgery

• &or uncomplicated hydatid disease morbidity and

mortality have been reported to be in the range of

'0E and 1E

• the long*term results of A!$ and surgery for hepatichydatid cysts are excellent. Most series report

recurrence rates less than 10E.

enign %epatic Masses

• The differential diagnosis of the benign solid hepatic

mass includes hepatic adenoma focal nodular

hyperplasia 7&)%8 focal fatty infiltration cavernous

hemangioma and other rare neoplasms 7e.g.

mesenchymal hamartoma and teratoma8

• enign hepatic lesions are common with an

estimated incidence of BE to GE and in one autopsy

series up to '0E of the population

2imple -ysts

• 2imple cysts are solitary more than ;0E of the time

and asymptomatic more than G0E of the time.

• 2i3e can range up to '0 cm although most are less

than ; cm• Asymptomatic simple cysts less than > cm reRuire no

intervention but should be observed

2imple -ysts

• Any symptoms are usually related to mass effect

causing pain in the right upper Ruadrant and

occasionally early satiety. $arely intracystic

hemorrhage and infection may develop

• patients with symptomatic cysts 7S; cm8 should

undergo laparoscopic or open cyst unroofing.

-omplex cysts

• !f multiple simple cysts are seen consider polycystic

liver disease

• This is an inherited condition 7autosomal dominant8

often found in association with renal cysts• the maDority of patients with polycystic liver disease

remain asymptomatic with preserved liver function

and do not reRuire surgical intervention

-omplex cysts

• iliary cystadenomas are uncommon slow*growing

complex cysts measuring up to '0 cm in si3e. They

are benign but have malignant potential to transform

into cystadenocarcinoma and thus should be

surgically removed whenever recogni3ed

• The diagnosis is made by the presence of

mesenchymal tissue

-omplex cysts

• $adiologically internal septations are almost always

seen in cystadenomas on contrast*enhanced ,T or

M1+. -ystadenomas have irregular borders and a

thick stromal layer and calcifications and mural

nodules can occasionally be seen in the walls

-omplex cysts

%emangioma

• Autopsy series report prevalances from 0.;E to as

high as '0.0E. The female*to*male ratio is between

;+1 and H+1. %emangioma is usually found between

the ages of =0 and B0 years

• tumors arise from the endothelial lining of blood

vessels as vascular ectasias and have been

associated with high estrogen states including

puberty pregnancy oral contraceptive use and

androgen treatment

%emangioma

• Most tumors are less than ; cm and asymptomatic

• -ontrast*enhanced -T with delayed venous

examination will demonstrate peripheral nodular

enhancement and progressive centripetal fill*in

%emangioma

• %emangiomas almost never reRuire surgical

resection after the diagnosis is secure because most

lesions are asymptomatic and risk of spontaneous

rupture is extremely small.

• &or symptomatic lesions simple enucleation is

recommended because it preserves the maximal

amount of functional liver

&ocal nodular hyperplasia 7&)%8

• -ocal nod%lar hyperplasia 2-*H8 is the second

most common benign solid hepatic tumor 7behind

hemangioma8 comprising >E of all primary hepatic

tumors.

• revalence of &)% is estimated to be =E of the

general population predominantly in women in their

third to fifth decades.

• The female*to*male ratio is between H+1 and >+1

&ocal nodular hyperplasia* &)%

• &)% consists of benign*appearing hepatocytes 4ith

cords of fibro%s septae radiating from a central

scar& 4hich comprises biliary str%ct%res of

hepatocell%lar origin

• Most patients present with an asymptomatic solitary

tumor of less than ; cm near the hepatic surface.

:nly 10E of patients have clinical symptoms

&ocal nodular hyperplasia *&)%

• :n contrast*enhanced multiphasic -T imaging

lesions are usually homogenous and isoattenuating

to liver parenchyma before contrast inDection. esions

are bright hypervascular with hypodense central

scarring on arterial phase examination. !f present

radiating hypodense fibrous bands and septa that

arise from the scar are characteristic findings

• )uclear medicine imaging can sometimes be helpful

to disting%ish -*H from hepatic adenoma

beca%se s%lfa(colloid is ta7en %p by %pffer cells

2present in -*H3& which are usually absent in

adenoma

• Treatment strategy is heavily influenced by the

certainty of diagnosis. !n asymptomatic patients with

a clear diagnosis no f%rther treatment is

necessary and the patient may be observed. !n

eRuivocal cases in which all imaging modalities fail to

establish a firm diagnosis& biopsy is 4arranted for

histologic examination

%epatic adenoma

• %epatic adenoma 7%A8 is a rare hepatic t%mor that

occurs predominantly in women aged '0 to (0 years

with a female*to*male ratio of at least (+1 and

reportedly as high as 11+1.

• !t has a strong association with oral contraceptive

use with an incidence of = to ( in 100000 oral

contraceptive users versus 1 in 100000 nonusers

%epatic adenoma

• %As are mostly solitary 7B0E,>0E8 wellcirc%mscribed& ro%nd& and %nencaps%lated. Apse%docaps%le is often present

• arger %A tumors 7S; cm8 can be associated with

right upper*Ruadrant pain fullness or discomfort.ecause of its hypervascular nature and lack of acapsule %A carries a moderate to high risk ofspontaneous rupture associated with increasing si3e7S; cm8. Jhen rupture occurs it is intratumoral in

one third of cases and intraperitoneal in two thirds ofcases.

%epatic adenoma

• /n ,T& adenomas often appear heterogeneous

because of their mixed components of fat&

hemorrhage& and necrosis. :n portal venous

examination or delayed images they may appear

isodense. %As are contrast enhancing because oftheir rich vascular supply and often show peripheral

enhancement with centripetal progression indicating

the presence of large subcapsular feeding vessels

and early draining veins

%epatic adenoma

Liver C$ner

Primary Liver ,ancer

• iver malignancy may arise from

– %epatocytes

– iliary epithelial cells

Malignant iver Tumors

1. %epatocellular carcinoma 7%--8

'. &ibro*lamellar carcinoma of the liver

=. %epatoblastoma

(. !ntrahepatic cholangiocarcinoma;. :thers

• A large proportion of patients will have intra* or extra*hepaticmetastases at presentation.

• infiltration of the portal venous system with subseRuentdissemination of tumor cells.

• asc%lar invasion is more common 4ith larger t%mors 2R !cm3.

• Most common mets include the hilar and celiac lymph nodes andthe lungsC metastases to bone and brain are less common andperitoneal disease 7ie carcinomatosis8

1is7 -actors ( H,,

• -hronic %" and %-"

• -irrhosis

• -hronic underlying liver disease.

1is7 -actors ( cholangio,A

• !nfreRuently associated with cirrhosis.

• rimary sclerosing cholangitis

• Jidespread infection with liver flukes 'Clonorchissinensis

23'A5C36A7CA7CI859A %--

%--+ !ncidence

• The most common primary liver cancer

• The most common tumor in 2audi men

• !ncreasing in U2 and all the world

%--+ $isk &actors

The most important risk factor is cirrhosis from any

cause+

1. %epatitis 7integrates in 4)A8

'. %epatitis -=. Alcohol

(. Aflatoxin

;. :ther

%--+ -linical &eatures

• Jt loss and $U pain 7most common8

• Asymptomatic

• Jorsening of pre*existing chronic liver dis

• Acute liver failure:?#+

• 2igns of cirrhosis

• %ard enlarged $U mass

• iver bruit 7rare8

%--+ Metastases

• $est of the liver

• ortal vein

• ymph nodes

• ung• one

• rain

%--+ 2ystemic &eatures

• %ypercalcemia

• %ypoglycemia

• %yperlipidemia

• %yperthyroidism

2igns / symptoms

• )onspecific symptoms)onspecific symptoms – abdominal pain

– &ever chills

– anorexia weight loss

– Daundice

• hysical findingshysical findings – abdominal mass in one third

– splenomegaly

– ascites

– abdominal tenderness

%--+ 4iagnosis

• -linical presentation

• #levated A&

• U2

• Triphasic -T scan+ very early arterial perfusion• M$!

• iopsy

%--+ labs

• abs of liver cirrhosis

A-P 2Alfa feto protein3

• !s an %-- tumor marker • "alues more than 100ng?ml are highly suggestive of

• #levation seen in more than B0E of pt

4iagnosis

' b) what investigations are reuired to !a"e a de#inite diagnosis

18 A& produced by B0E of %--

S (00ng?ml

A& over time

'8 !maging

* focal lesion in the liver of a patient with cirrhosis is highly likely

to be %--

* 2piral -T of the liver

* M$! with contrast enhancement

4iagnosis

=8 iopsy is rarely reRuired for diagnosis

in 1,=E.

iopsy of potentially operable lesions

should be avoided where possible

,eedin

U2+ %--

-T+ "enous hase

-T+ Arterial hase

4iagnosis

Cirr*o,i, @ M$,, ! /

R$i,ed

Nor/$-

A,,e,, for

,urer+

CT% MRI

-e,ion &+ e3$/

FNAC or &io,+Confir/ed

di$no,i,

Liver C$ner Tre$t/ent

Treatment 72urgery8

• The only proven potentially curative therapy for %--

The only proven potentially curative therapy for %--

• Hepatic resection or liver transplantation

• atients with single small %-- 7; cm8 or up to three lesions = cm

• !nvolvement of large vessels 7portal vein !nferior vena cava8 doesntautomatically mitigate against a resectionC especially in fibrolamellarhistology

• *o randomised controlled trials comparing the o%tcome ofs%rgical resection and liver transplantation for H,,.

Treatment 72urgery8

• %epatic resection should be considered in %-- and a non*cirrhotic

%epatic resection should be considered in %-- and a non cirrhotic

liver 7including fibrolamellar variant8

• $esection can be carried out in highly selected patients with

cirrhosis and well preserved hepatic function 7-hild*ugh A8 who are

unsuitable for liver transplantation. !t carries a high risk of

postoperative decompensation.

• erioperative mortality in experienced centres remains between HE

and '0E depending on the extent of the resection and the severity of

preoperative liver impairment.

• The maDority of early mortality is due to liver failure.

Treatment 72urgery8

• $ecurrence rates of ;0,H0E after ; years after resection are usual7intrahepatic8

• iver transplantation should be considered in any patient with

cirrhosis

• atients with replicating %"? %-" had a worse outlook due to

recurrence and were previously not considered candidates for

transplantation.

• #ffective antiviral therapy is now available and patients with small%-- should be assessed for transplantation

Treatment 7non*2urgical8

should only be used where surgical therapy is not possible.

#3 Perc%taneo%s ethanol in8ection 2PE+3

• has been shown to produce necrosis of small %--.

• !t is best suited to peripheral lesions less than = cm in

diameter

53 1adiofreN%ency ablation 21-A3

• %igh freRuency ultrasound to generate heat

• good alternative ablative therapy

• )o survival advantage

• Useful for tumor control in patients awaiting liver transplant

=3 ,ryotherapy

• intraoperatively to ablate small solitary tumors outside a

planned resection in patients with bilobar disease

>3 ,hemoembolisation

• -oncurrent administration of hepatic arterial chemotherapy

7doxirubicin8 with emboli3ation of hepatic artery

• roduce tumour necrosis in ;0E of patients

• #ffective therapy for pain or bleeding from %--• Affect survival in highly selected patients with good liver

reserve

• -omplications+ 7pain fever and hepatic decompensation8

!3 Systemic chemotherapy

– very limited role in the treatment of %-- with pooresponse rate

– est single agent is doxorubicin 7$$+ 10* '0E8

– -ombination chemotherapy didn6t response butsurvival

– should only be offered in the context of clinical trials

$3 Hormonal therapy- )olvadex stilbestrol and flutamide

I3 +nterferon(alfa

B3 retinoids and adaptive imm%notherapy 2ad8%vant8

%--+ ocal Ablation

• &or non resectable pt

• &or pt with advanced liver cirrhosis

• Alcohol inDection

• $adiofreRuency ablation• Temporary measure only

$adio &reRuency Ablation

#thanol !nDection

-hemoemboli3ation

• !nDect chemotherapy selectively in hepatic artery

• Then inDect an embolic agent

• :nly in pt with early cirrhosis

• )o role for systemic chemotherapy

-hemoemboli3ation

%--+ rognosis

• Tumor si3e

• #xtrahepatic spread

• Underlying liver disease

• t performance status

%--+ iver

Transplantation

p• est available treatment

• $emoves tumor and liver

• :nly if single tumor less than ;cm or less than = tumors

less than = cm each

• $ecurrence rate is low

• )ot widely available

2election of agents for targeted

therapy in %--*ame Target

;efitinib

Erlotinib

Lapatanib

,et%ximab

6evaci'%mabSorafenib 2*exavar3

S%nitinib

atalanib

,ediranib

1apamycin

Everolim%s

6orte'omib 2elcade3

E;-1af#& 6(1af& E;-1 & PD;-1

PD;-1& E;-1& c(+T& -LT(<

E;-1& PD;-1& c(+T

mT/1 2mammalian target of rapamycin8

Proteasome

Targeting angiogenesis for %--

• %-- is one of the most vascular tumor %-- is one of the most vascular tumor

• MaDor driver of angiogenesis is vascular endothelial growthMaDor driver of angiogenesis is vascular endothelial growth

factor 7"#9&8factor 7"#9&8

• 2orafenib and bevace3umab target "#9& in %--2orafenib and bevace3umab target "#9& in %--

• evaci3um3b+ Median :2 of approximately 1' monthsevaci3um3b+ Median :2 of approximately 1' months

• evaci3umab V erlotinib+ Medain :2 1;*1B monthsevaci3umab V erlotinib+ Medain :2 1;*1B months

!nvestigational combination therapies

in %--

• -ombinations under investigations-ombinations under investigations

– evaci3um3b V erlotinib

– 2orafenib Verlotinib

• -ombination therapy will likely be used to treat %---ombination therapy will likely be used to treat %--

in the futurein the future

,linical +mportance of Early Detection

@ Precise staging of H,,

•T8> Re,etion

A&-$tion

FT!> Tr$n,-$nt

• 2+r ,urviv$- r$te,

2# 0 B#

F 'CC, deteted in T8 1 T! ,t$e, ,*o7 /u* &etter ,urviv$-

F Sen,itive i/$in /od$-itie, to detet 'CC, in it, e$r-+ ,t$e,E-Ser$ '5% et $-. G$,troentero-o+ !##? 84">8B2!8B94.

iver failure+

• iver failure+

-linical syndrome+ sudden loss of

liverparenchymal and metabolic function

Manifest as coagulopathy and

encephalopathy

iver failure

'+er $ute -iver f$i-ure

Su& $ute -iver f$i-ure

#o$et r!% o& "ere'ral oede(a)

e*"ephalopathy

+a!ly "o*&ed $!th C#D"!te

#o$et "ha*"e o& po*ta*eo

Aute -iver f$i-ure/reatet r!% o& "ere'ral

oede(a, CS &a!lre

/reatet "ha*"e o&

po*ta*eo r!al

Multi systemdisease ,oag%lopathy

• !)$ important prognostic indicator in established A&

• latelet dysfunction 4!- * rare Metabolic

• !nsulin resistance + -larke et al %epatology• %yperlactataemia +Bernal et al ancet (##( ) use%ul to trac*

• iver net producer of lactate Murphy et al Crit Care Med(##+

• 0( Mg )a glucose O p%• %igh incidence of pancreatitis

*%trition

• &reRuent poor recent oral intake W vomiting• )o evidence for protein restriction in either acute or

-4• 9astric prophylaxis

Acute liver failure

• Acute liver failure +

4efined as interval between onset of the illness and

appearance of encephalopathy N > weeks

Acute liver failure +

• #tiology+

+ heterogenous drugs

7acetaminophen )2A!48 viruses

+ viruses regional4ifference 7endemic area <8

Acute liver failure

• Uncommon causes+

Jilson6s disease other infections 7-M" %2"

#"8 vascular abnormality toxin acute fatty liver

of pregnancy antoimmune hepatitis ischemiamalignant infiltration

Acute liver failure

• 2ymptoms and signs+

Iaundice altered mental status nausea?

vomiting anorexia fatigue malaise

myalgia?arthralgiaMost of them present hepatoencephalopathy

and icteric appearance.

)on*specific Management

%ypoglycemia

#ncephalopathy

!nfections

%emorrhage-oagulopathy

%ypotension7hypovolemia vascular resistance X8

$espiratory failure

$enal failureancreatitis

• %ypoglycemia+ monitoring blood glucose !" glucose

supplement.

• !nfection+ aseptic care high index of suspicion

preemptive antibiotic.

• %emorrhage 7i.e. 9!8+ )9 placement %' blocker or

• %ypotension+ hemodynamic monitoring or central

pressures volume repletion

• $espiratory failure 7A$428+ mechanical ventilation.

• $enal failure 7hypovolemia hepatorenal syndrome

AT)8+ hemodynamic monitor central pressure

volume repletion avoid nephrotoxic agent

#ncephalopathy

• maDor complication

• precise mechanism remains unclear

• %ypothesis+ Ammonia production

• Treatment toward reducing ammonia production• Jatch out airway prevent aspiration

#ncephalopathy ortal 2ystemic #ncephalopathyortal systemic shunt

– spontaneous collateral – 2urgical – T!2

%# of Acute iver &ailure

%epatocellular failure

$apid onset-erebral oedema

Myoinositol levels not reduced

-ytotoxic and vasogenic

)ot at risk of cerebral oedema

recipitating factors

– 2epsis

• 2 $x fluids VV• Albumin

• Avoid renal failure

– -)2 active drugs

– #lectrolyte abnormalities – 4iuretics * over use

– 9astrointestinal bleeding

#ncephalopathy

• 2tage 1+ day*night reversal mild confusion

somnolence

• 2tage '+ confusion drowsiness

• 2tage =+ stupor

• 2tage (+ coma

#ncephalopathy

redisposing factor of hepatic encephalopathy+

9! bleeding increased protein intake hypokalemic

alkalosis hyponatremia infection constipation

hypoxia infection sedatives and tranRuili3ers

#ncephalopathy

T %pon ammonia hypothesis

• -orrection of hypokalemia

• $eduction in ammoniagenic substrates+ cleansing

enemas and dietary protein restriction.

• Lact%lose improved encephalopathy& b%t not

improved o%tcome.

4ose '*= soft stools per day

#ncephalopathy

: l tibi ti i l k f id

• :ral antibiotics+ neomycin lack of evidence

nephrotoxicity limited use.

%epatic #ncephalopathy%epatic #ncephalopathy

F $tage 1% shorted attention span& reversal of sleep(4a7e

cycle& s%btle personality changes 2anxiety& irritability3

F $tage 2% lethargy& personality change& disorientation.

Asterixis.

F $tage &% st%por b%t responsive& severe conf%sion and

disorientation& abnormal behavio%r& incomprehensible

speech

F $tage '% coma

-erebral #dema

- b l d d l i B; >0 E f ti t

• -erebral edema develops in B; * >0 E of patients

with grade !" encephalopathy.

• precise mechanism + not completely understood

• ossible contributing factor +

1*osmotic derangement in astrocytes

'*changes in cellular metabolism

=*alterations in cerebral blood flow

-erebral #dema

-li i l if t ti

• -linical manifestations+

Yintracranial pressure 7!-8 and brainstem

%erniation the most common causes of death

in fulminant hepatic failureischemic and hypoxic inDury to the brain

hypertension bradycardia and irregular

respirations Y muscle tone hyperreflexia

-oagulopathy

di i i h d it f th f ili li t th i

• diminished capacity of the failing liver to synthesi3e

coagulation factors.

• The most common bleeding site+ 9! tract.

• rophylactic administration of &&+ not

recommended.

performed before transplant or invasive procedure

iver transplant

i t l t i b kb f t t t f

• iver transplant+ remain backbone of treatment of

fulminant hepatic failure

reliable criteria to identify these patients who really

need transplant.

remain unresolved in fulminant hepatic failure.

iver support system

* ll b d

• *on(cell(based

• plasmapheresis and charcoal*based

hemoabsorption

• ,ell(based systems

• known as bioartificial liver support systems

• *on(cell(based not improved s%rvival.

Available systems

• 2MA1S3 Molec%lar Adsorbents 1ecirc%lationSystem

iver 4ialysis

ridge to transplant

• ridge to transplant

• 4ialy3e H hours at a time

Molec%lar Adsorbents1ecirc%lation System

2MA1S3 L

MA$2 Therapy

& encephalopathy

• -ontrols+ biochemistry static worsening

encephalopathy

Co$u-o$t*+ $nd

MARS tre$t/ent in CLD

Sin-e P$,, A-&u/in Di$-+,i, (SPAD)

C-e$r$ne of &i-iru&in% &i-e $id,% N'" > i/roved

• Significant improvement in encephalopathy

• *o change in renal f%nction or creatinine

• *o change in ammonia or cyto7ine levels 2T*-& +L($& +L(#"& +L(B3&

MDA& MELD fell in both gro%ps

*o differences in s%rvival

LIVER TRANSPLANT

i T l t ti

iver Transplantationfor

Alcoholic iver 4iseaseLiver

Transplantation

Live Donor Liver Tr$n,-$nt

iver transplant complications

• 1e8ection. Abo%t I"C of all liver(transplant patients

have some degree of organ re8ection prior to

have some degree of organ re8ection prior todischarge.

• Anti(re8ection medications are given to 4ard off theimm%ne attac7.

• +nfection• Most infections can be treated s%ccessf%lly as they

occ%r.

• ,ancer

iliary -omplications ,-he Achilles heel o% li.er

transplantation/

• Early 2 <" days3

Anastomotic bile lea7

Anastomotic strict%re

6ile lea7 at T t%be exit

/bstr%ction of T t%be

Sphincter of /ddidysf%nction

• Late 2R <" days3

Anastomotic strict%re

*onanastomotic

strict%res

6ile lea7 on T t%be

removal

Sphincter of /ddi

dysf%nction

!"#$%'$

PAA UUUUUUU(((;ATA FFFF

G$--&-$dderG$--&-$dder

Di,order,Di,order,

A)AT:MZ / %Z2!::9Z

6+L+A1) S)STEM

6+L+A1) S)STEMa.,analic%li the smallest bile ducts located

between liver lobules receive bile fromhepatocytes. The canaliculi form larger bileducts which lead to hepatic duct.

b.Hepatic d%ct , from the liver Doins the cysticduct from the gallbladder to form the commonbile duct which empties into the duodenum.

c.Sphincter of /ddi , controls the flow of bileinto the intestine.

d.;allbladder , is a hollow pear*shaped organthat is =0*(0mm long. )ormally holds =0*;0mof bile and can hold up to B0m when fullydistended.

!!A$Z 2Z2T#M

• Draining bile from hepatocytes to the gallbladder

Draining bile from hepatocytes to the gallbladderby 4ay of biliary tree

• 2toring bile in the gallbladder and releasing it to the

duodenum which is mediated by the hormone

cholecysto7inin(pancreo'ymin.

• 2tores and concentrates bile

2tores and concentrates bile

• -ontracts during the digestion of fats to deliver the

• Cholecysto"inin is released by the duodenal cells

causing the contraction of the gallbladder andrelaxation of the sphincter of /ddi

C'OLELIT'IASIS

-%:#!T%!A2!2

• 1efers to formation of calc%li 2ie

• 1efers to formation of calc%li 2ie&gallstones in the bladder .

• redisposing &actors+1.:bese

'.&emale

=.S(0 yrs

(.:- #strogen intake;.&air

-%:#!T%!A2!2

Su!ersaturate bile "iliaryt i

Su!ersaturate bile, "iliarystasis

Stone formation

"locage of Gallblaer

In)ammation, 9ucosal amage an"C in(ltration

9all 2tones

-%:#-Z2T!T!2

, inflammation of gallbladder with gallstone formation.

inflammation of gallbladder with gallstone formation.

-%:#-Z2T!T!2?

-%:#!T%!A2!2

Signs and Symptoms

Signs and Symptoms• Severe 1ight abdominal pain radiating to the

bac7• -ever

• -at intolerance• Anorexia& n=v• 9a%ndice• Pr%rit%s• Easy br%ising

• Tea colored %rine• Steatorrhea

-holecystitis / -holelithiasis

by+ 9ari 9laser

Jhat is it<

• y definition

cholecystitis is an

inflammation of the

gallbladder wall and

nearby abdominallining.

A&do/in$- 7$-- G$--&-

#tiology ? athophysiology

• -an be caused by an obstruction gallstone or a tumor.

• G0E of all cases caused by gallstones.

• The exact cause of gallstone formation is un*no0n.

*en t*ere i, $n o&,trution% $--,tone or

tu/or it revent, &i-e fro/ -e$vin t*e

$--&-$dder. 5i-e et, tr$ed $nd $t, $, $n irrit$nt 7*i* $u,e,

e--u-$r infi-tr$tion 7it*in 4 0 " d$+,.

• This infiltration causes an

inflammatory process , the

y pgallbladder becomes

enlarged and edematous.

• #ventually this

occlusion along withbile stasis causes the

mucosal lining of the

gallbladder to become

necrotic.

• acterial growthoccurs due to

ischemia.

Neroti

G$--&-$dder

• $upture of the gallbladder becomes a danger along with spread

of infection of the hepatic duct and liver.

• !f the disease is severe and interferes with the blood supply it

can cause the gallbladder to become gangrenous.

enou,$--&-

G$--,t

9allstones . .

• The presence of

gallstones in the

gallbladder is called

cholelithiasis.

Those who are most at risk.

• These are all adDectives to describe the person most at

risk of developing symptomatic gallstones.

p g y p g

FAIR FAT FORT FEMALE

2igns and 2ymptoms.

• -omplaints of indigestion after

eating high fat foods. li d i i th i ht

• ocali3ed pain in the right*

upper Ruadrant epigastric

region.

• Anorexia nausea vomiting

and flatulence.

Inre$,ed *e$rt $nd re,ir$tor+ r$te 0$u,in $tient to &eo/e di$*oreti

7*i* in turn /$6e, t*e/ t*in6 t*e+

$re *$vin $ *e$rt $tt$6.

2igns and 2ymptoms.

• ow grade fever.

g• #levated leukocyte count.

• Mild Daundice.

• 2tools that contain fat , steatorrhea.

• -lay colored stools caused by a lack of bile in the

intestinal tract.

• Urine may be dark amber* to tea*colored.

4iagnostics.• &ecal studies.

• 2erum bilirubin tests.

• Ultrasound of thegallbladder.

4iagnostics.

• %!4A scan * imaging test used to

examine the gallbladder and the ductsleading into and out of the gallbladder * also

leading into and out of the gallbladder also

referred to as cholescintigraphy.

• :ral cholecystogram * the

patient takes iodine*containing tablets by

mouth * iodine is absorbed from the

intestine into the bloodstream * removedfrom the blood by the liver and excreted by

the liver into the bile , it is concentrated in

the gallbladder * outlines the gallstones that

are radiolucent 7x*rays pass through them8.

• :perative cholangiography , common bile duct is directly inDected withradiopaRue dye.

$ecap. 2tages of Acute -holecystitis.

- G$--&-$dder *$, $ r$+i,*

$e$r$ne 1 i, ede/$tou,.

-T*ere i, $n o&,trution of t*e

+,ti dut $nd t*e $--&-$dder

&ein, to ,7e--.

- It no -oner *$, t*e ro&in

e &-ue $e$r$ne of $

nor/$- $--&-$dder.

A, $ute *o-e+,titi,

rore,,e,% t*e $--&-$dder

&ein, to &eo/e neroti

$nd et, $ ,e6-ed

$e$r$ne $, t*e 7$--&ein, to die.

- G$--&-$dder underoe,

$nrenou, *$ne $nd

t*e 7$-- &eo/e, ver+

d$r6 reen or &-$6.

- T*i, i, t*e ,t$e 7*en

erfor$tion our,.

Medical Management.

• ithotripsy• for patients with only

If t*e $tt$6 of

*o-e-it*i$,i, i, /i-d 0

a FE1 stones. &ed re,t i, re,ri&ed.

$tient i, -$ed on

NPO to $--o7 GI tr$t

$nd $--&-$dder to re,t. $n NG tu&e i, -$ed

on -o7 ,ution.

f-uid, $re iven IV in

order to re-$e -o,t

f-uid, fro/ NG tu&e

,ution.

Medical Management.

,holecystectomy

Laparoscopic ,holecystectomy

, removal of the gallbladder.

This is the treatment of choice.

The gallbladder along with the cysticduct vein and artery are ligated.

Medical Management.• !f stones are present in the

common bile duct anendoscopic sphincterotomy m st be performed to remo e

must be performed to removethem BEF23E acholecystectomy is done.

• A number of various

instruments are insertedthrough the endoscope inorder to [cut[ or stretch thesphincter.

• :nce this is done additionalinstruments are passed thatenable the removal of stonesand the stretching ofnarrowed regions of theducts.

• 4rains 7stents8 can also beused to prevent a narrowedarea from rapidly returning toits previously narrowed state.

Jill you survive<

• rognosis is usually excellent with prompt treatment.

• aparoscopic surgery has decreased the number of

complications.

• rognosis is ):T favorable for those who develop

pancreatitis.

!6ll leave you with these.

-%:#!T%!A2!2?-%:#-Z2T!T!2

• 2urgical procedures* 2urgical -holecystectomy-h l d h t

-holedochotomy

• aparoscopic cholecystectomy

!"#$%'$

L+E1 D+SEASE

T*e future>

Inre$,in -iver di,e$,e

$-o*o-% 'CV% NAFLD

Tre$t/ent *$nin

Innov$tive tre$t/ent otion,

-iver ,uort ,+,te/, furt*er

Contro--ed tri$-, re;uired

Tr$n,-$nt$tion i, $ re$- otion

E$r-+ di,u,,ion

A,,u/e f-uid de-ete> ti/e i, ti,,ue

Infetion i, o//on

Ait$tionH'E

C-o,e o&,erv$tion

PATH/L/;) /- THEPATH/L/;) /- THE

PA*,1EASPA*,1EAS

PA*,1EASPA*,1EAS##

++. Detailed Anatomy

A. andmark structures

1. 2plenic Artery+

a. ranch of celiac

b. passes right to

c. -ourse is along

upper margin ofbody and tail

Arterial S%pply to Pancreas

Co!!on

Hepatic (rtery

roper Hepatic

(rtery

$uperior

*esenteric

(rtery

Detailed Anatomy contin%ed

. Head of Pancreas

+ Head , ody and Tail o# ancreas

1+ .!portant clinically because%a+ Nu!erous ducts and vessels traverse it

b+ Carcino!a usually located here

D%ct of irs%ng 2Main pancreatic d%ct3

D+SEASES /- THED+SEASES /- THEP A * , 1 E A SP A * , 1 E A S

• ,ongenital anomalies,ongenital anomalies – Agenesis& hypoplasia& ectopia& d%ct anomaliesAgenesis& hypoplasia& ectopia& d%ct anomalies

• Exocrine pancreasExocrine pancreas

p – ,ystic fibrosis,ystic fibrosis

– Ac%te pancreatitisAc%te pancreatitis

– ,hronic pancreatitis,hronic pancreatitis

– ,arcinoma of the pancreas,arcinoma of the pancreas• Endocrine pancreasEndocrine pancreas

– Diabetes mellit%sDiabetes mellit%s

– +slet cell t%mors+slet cell t%mors

.V+ ancreatic /isorders

(+ ancreatitis% diagnosis depends on

clinical evidence

1+ 0sually secondary to biliary tract

disease

2+ $urgery o# biliary tract or sto!ac

alcoholis! are other causes

D+SEASES /- THE E/,1+*E PA*,1EASD+SEASES /- THE E/,1+*E PA*,1EASA,TE PA*,1EAT+T+SA,TE PA*,1EAT+T+S

• +nflammation of the pancreas& 4hich is almost al4ays+nflammation of the pancreas& 4hich is almost al4aysassociated 4ith acinar cell in8%ryassociated 4ith acinar cell in8%ry

• A clinical @ histologic spectr%m of severity @ d%rationA clinical @ histologic spectr%m of severity @ d%ration

• Etiologic factorsEtiologic factors

– #3 Metabolic#3 Metabolic alcohol&alcohol& hyperlipoproteinemia&hyperlipoproteinemia&hypercalcemia& dr%gs 2e.g. thia'ides3& genetichypercalcemia& dr%gs 2e.g. thia'ides3& genetic

– 53 Mechanical53 Mechanical gallstones&gallstones& tra%matic @ perioperativetra%matic @ perioperativein8%ryin8%ry

– <3 asc%lar shoc7& atheroembolism& polyarteritis<3 asc%lar shoc7& atheroembolism& polyarteritisnodosanodosa

– >3 +nfections M%mps& ,oxsac7ie vir%s& Mycoplasma>3 +nfections M%mps& ,oxsac7ie vir%s& Mycoplasma – !3 +diopathic #"(5"C O F ;enetic basis!3 +diopathic #"(5"C O F ;enetic basis

• PathologyPatholo

gy –

> basic alterations> basic alterations• #3 Proteolytic destr%ction of pancreatic s%bstance#3 Proteolytic destr%ction of pancreatic s%bstance• 53 *ecrosis of blood vessels @ interstitial hemorrhage53 *ecrosis of blood vessels @ interstitial hemorrhage

• 53 *ecrosis of blood vessels @ interstitial hemorrhage53 *ecrosis of blood vessels @ interstitial hemorrhage• <3 -at necrosis by lipolytic en'ymes<3 -at necrosis by lipolytic en'ymes• >3 Associated ac%te inflammatory reaction>3 Associated ac%te inflammatory reaction

– Pathologic lesionsPathologic lesions• a. Ac%te pancreatic necrosisa. Ac%te pancreatic necrosis• b. Ac%te hemorrhagic pancreatitisb. Ac%te hemorrhagic pancreatitis• c. S%pp%rative peritonitisc. S%pp%rative peritonitis• d. Pancreatic pse%docystsd. Pancreatic pse%docysts

• PathogenesisPathogenesis

– A%todigestion of pancreatic tiss%e by inappropriatelyA%todigestion of pancreatic tiss%e by inappropriatelyactivated pancreatic en'ymesactivated pancreatic en'ymes

– TrypsinTrypsin has a ma8or rolehas a ma8or role• a. Activates other proen'ymesa. Activates other proen'ymes 2proelastase2proelastase &&prophospholipase 3prophospholipase 3• b. ,onverts pre7alli7rein to 7alli7rein 2inin system3b. ,onverts pre7alli7rein to 7alli7rein 2inin system3• c. Hageman factor is activatedc. Hageman factor is activated

– Mechanisms of pancreatic en'yme activationMechanisms of pancreatic en'yme activation• #3 Pancreatic d%ct obstr%ction#3 Pancreatic d%ct obstr%ction• 53 Primary acinar cell in8%ry53 Primary acinar cell in8%ry• <3 Defective intracell%lar transport of proen'ymes 4ithin acinar cells<3 Defective intracell%lar transport of proen'ymes 4ithin acinar cells

• ,linical feat%res,linical feat%res

– Abdominal pain is the cardinal manifestation epigastric& radiatingAbdominal pain is the cardinal manifestation epigastric& radiatingto bac7& variable in severityto bac7& variable in severity

Sh 7 d t ti h h @ l f dil tSh 7 d t ti h h @ l f dil t

– Shoc7 d%e to pancreatic hemorrhage @ release of vasodilatoryShoc7 d%e to pancreatic hemorrhage @ release of vasodilatoryagents 26 @ P;s3agents 26 @ P;s3

• LabLab ↑

ser%m amylase and lipaseOser%m amylase and lipaseO↓

,aO,aO

bilir%bin&bilir%bin&↑

gl%cose @ glycos%riagl%cose @ glycos%ria• ,T scan,T scan inflammation& pse%docystsinflammation& pse%docysts

• PxPx severe cases have high mortality rate 25"(>"C3severe cases have high mortality rate 25"(>"C3

• Death d%e toDeath d%e to #3 shoc7& 53 secondary abdominal#3 shoc7& 53 secondary abdominalsepsis& <3 ad%lt respiratory distress syndromesepsis& <3 ad%lt respiratory distress syndrome

D+SEASES /- THE E/,1+*E PA*,1EASD+SEASES /- THE E/,1+*E PA*,1EAS,H1/*+, PA*,1EAT+T+S,H1/*+, PA*,1EAT+T+S

• 1epeated bo%ts1epeated bo%ts of mild to moderate pancreaticof mild to moderate pancreatic

inflammation& 4ith contin%edinflammation& 4ith contin%ed lossloss of pancreaticof pancreaticparenchyma @ replacement byparenchyma @ replacement by fibro%sfibro%s tiss%etiss%e

• Distinction from ac%te pancreatitisDistinction from ac%te pancreatitis may bemay bediffic%ltO distinction is made if there is evidence ofdiffic%ltO distinction is made if there is evidence ofprevio%s attac7sprevio%s attac7s

• Middle(aged men& mostly inMiddle(aged men& mostly in alcoholicsalcoholics b%t mayb%t mayd%e to biliary tract disease& hyperlipoproteinemiad%e to biliary tract disease& hyperlipoproteinemia@ hypercalcemiaO no apparent ca%se in !"C of@ hypercalcemiaO no apparent ca%se in !"C ofcasescases

• PathogenesisPathogenesis+ – Protein hypersecretion from acinar cellsProtein hypersecretion from acinar cells – Precipitation of proteins forming d%ctal pl%gsPrecipitation of proteins forming d%ctal pl%gs – Pl%gs enlarge forming laminar aggregatesPl%gs enlarge forming laminar aggregates

D+SEASES /- THE E/,1+*E PA*,1EASD+SEASES /- THE E/,1+*E PA*,1EAS,H1/*+, PA*,1EAT+T+S,H1/*+, PA*,1EAT+T+S

• PathologyPathology – Hard organ 4ith dilated d%cts @ calcified concretionsHard organ 4ith dilated d%cts @ calcified concretions – -ibrosis& chronic inflammatory cells& obstr%ction of-ibrosis& chronic inflammatory cells& obstr%ction of

d%cts by protein pl%gsd%cts by protein pl%gs

d%cts by protein pl%gsd%cts by protein pl%gs – Extensive atrophy of exocrine glandsExtensive atrophy of exocrine glands – Pse%docystsPse%docysts

• ,linical feat%res,linical feat%res – 1epeated attac7s of abdominal pain or may be silent1epeated attac7s of abdominal pain or may be silent• DxDx clinical s%spicion& lab @ ,Tclinical s%spicion& lab @ ,T• PxPx chronic disabling disease d%e to its ma8orchronic disabling disease d%e to its ma8or

complications pancreatic ins%fficiency @ diabetescomplications pancreatic ins%fficiency @ diabetes

mellit%smellit%s

ancreatic /iseases, continued

/ Chronic ancreatitis

/+ Chronic ancreatitis

1+ organ usually appears as

s!all, atrophic

2+ Contains scattered echoes

#ro! calci#ications&+ ri!ary cause is alcoholis!

E /ilation o# ancreatic /uct

E+ /ilation o# ancreatic /uct

1+ $een in acute or chronic

pancreatitis

2+ reuently associated with

neoplas! o# pancreas

&+ iliary tract proble!s

(bscess or He!orrhagic ancreatitis

+ (bscess or He!orrhagic ancreatitis

1+ $i!ilar in sonographic appearance

2+ He!orrhagic% a+ *ass with inho!ogeneous te3ture

b+ (cute he!orrhage% sonolucent to

echogenic

c+ CT scan used #or di##erentiation

4+ ancreatic Tu!ors

1+ *alignant tu!ors usually arise

as adenocarcino!as

2+ .n head o# ancreas% $3

a+ ainless 5aundiceb+ (nore3ia

ancreatic Tu!ors, .n head, continued

c+ Nausea

d+ 6eight loss

e+ .ncreased plas!a a!ylase#+ .ncreased al"aline phosphatase

g+ *ay involve co!pression o#

pancreatic duct, C/

ancreatic Tumors in the %ead

• Tumors in the head

may compressbiliary ducts or

pancreatic ducts

ancreatic tu!ors, continued

&+ .n ody o# ancreas% $3 a 4nawing pain radiating to bac"

a+ 4nawing pain radiating to bac"

b+ ain increases a#ter eating or

lying downc+ 6eight loss, anore3ia

d+ 7arge tu!or !ay co!press

.VC, portal vein

ancreatic tu!ors,

continued

'+ .n Tail o#

ancreas% $3

a+ O#ten silent until

local !etastasis occurs

b+ *ay !etastasi8e to%

1+ para-aortic ly!ph

2+ spleen

9+ .denti#ied by organ enlarge!ent,

subtle echo changes, irregular outline

:+ *etastases to sto!ach, liver ; lungs

are co!!on

<+ O#ten causes dilation o# ducts

ancreatic /isorders, continued

H+ ibrocystic /isease

1+ =esult o# cystic #ibrosis2+ /iagnosed by !ethods other than

ultrasound

.+ ancreaticolithiasis

1 Ch t i ti t h i ti

1+ Characteristic stone echoes in pancreatic

2+ *ay see atrophied pancreatic parenchy!a

&+ (ssociated with chronic alcoholic

pancreatitis

'+ Contours o# body, tail show irregularities

ancreatolithiasis, continued

9+ .ncidence slightly higher in head

:+ (ssociated with occult pancreatic

carcino!a

a+ *ass > 2!! dia!eter

b+ $een with dilation o# pancreatic

duct or C/

-*,T+/*=D)S-*,T+/* /-

E*D/,1+*E PA*,1EAS

4iabetes

Endocrine unction %

Cells o# the .slet o# 7angerhans

synthesi8e and release hor!ones into

the circulation+

Hor!ones travel through the bloodstrea!

to target tissues Aespecially liver and

!uscle)

(t the target cells, hor!ones bind speci#ic

receptors and cause cell changes thatcontrol !etabolis!

Pancreatic endocrine cells reg%latecarbohydrate& fat& protein metabolism

– Alpha cells , secrete the hormonel

glucagon

– 6eta cells , secrete the hormones insulin

and amylin – Delta cells , secrete the hormones

gastrin and somatostatin

– - cells * secrete hormone pancreaticpolypeptide

6eta ,ells

$ynthesi8e pre-proinsulin, a protein

This is cleaved by en8y!es → proinsulin,

then cleaved again → insulin

.nsulin is the biologically active hor!one

that is released into the bloodstrea!

!nsulin secretion is controlled

through several mechanisms+

• ,hemically , high levels of glucose and amino acidsin the blood

• Hormonally , beta cells are sensitive to several

hormones that may inhibit or cause insulin secretion

• *e%rally , stimulation of the parasympatheticnervous system causes insulin to be secreted.

!nsulin secretion is decreased by+F /ecreased blood glucose

concentrationF .ncreased blood insulin

concentrationF $y!pathetic sti!ulation

!nsulin• Transported through the blood to target tissues where

it binds to specific receptors

• The binding of insulin to target cells+ – Acts as a biochemical signal to the inside of the cell

• :verall cell metabolism is stimulated

:verall cell metabolism is stimulated

• There is increased glucose uptake into the cell

• $egulation of glucose breakdown within the cell• $egulation of protein and lipid breakdown within

the cell

• lood glucose is decreased because insulin causesglucose to leave the bloodstream and enter the

metaboli3ing cells.

• Jith the exception of brain liver and erythrocytes

tissues reRuire membrane glucose carriers.

4isorder 4iabetes mellitus‑

• The single most common endocrine disorder , groupof glucose intolerance disorders

• !ncidence is estimated at 1*'E of the )orth American

population

• Many of these cases are undiagnosed

4iabetes mellitus

Historically distinguished by weight‑

loss, e3cessive urination, thirst, hunger

E3cessive urination polyuria

E3cessive thirst polydipsiaE3cessive hunger polyphagia

*odern characteri8ation is by

hyperglyce!ia and other !etabolicdisorders

*odern classi#ications ATable1<+<)

Type 1 or .//* .nsulin /ependent /iabetes‑

*ellitus

Type 2 or

N.//* Non .nsulin /ependent /iabetes‑ ‑

*ellitus

Other Types o# /iabetes *ellitus

4/* 4estational /iabetes *ellitus‑

-linical Manifestations+;l%cose in %rine( ecause when insulin is not present

glucose is not taken up out of the blood at the target

cells.

2o blood glucose is very highly increased increased

glucose filtered and excreted in the urine 7exceeds

transport maximum8

-linical Manifestations+eight loss ( atient eats but nutrients are not taken up

by the cells and?or are not metaboli3ed properly

/smotic di%resis results in fluid loss

f b d ti b t b li f f t d t i

oss of body tissue by metabolism of fats and proteins

olyuria, polydipsia, pholyphagia

Detoacidosis

ats and proteins are !etaboli8ed

e3cessively, and byproducts "nown as"etone bodies are produced+ These are

"etone bodies are produced+ These are

released to the bloodstrea! and cause%

/ecreased pH Aso increased acidity)Co!pensations #or !etabolic

acidosis

(cetone given o## in breath

1+ (d!inister insulin

*ay be o# ani!al or hu!an originCannot be given orally

Treatment

atient !ust !onitor their blood

glucose concentration and

ad!inister insulin with the correct

ti!ing

2+ Control diet Carbohydrates should !a"e up

about 99-:@ o# patientFs total

caloriesats should !a"e up >&@ o#

ti tF t t l l i

patientFs total calories

roteins should !a"e up about 19-

2@ o# patientFs total calories

&+ *onitor e3ercise

=e!e!ber% !uscles are a target tissue o#

insulin, and !etaboli8e !uch glucose #or

energy

$o!eti!es e3ercise →irregular blood

glucose levels $o diabetic patients shouldbe !onitored when they are e3ercising

Other%

ancreatic transplant G so #ar not

success#ul E3peri!ental therapies G not as

success#ul as hoped

Type ' or )!44M

*ore co!!on than .//*, o#ten

undiagnosed

.t has a slow onset *ost co!!on in those '@ years,

*ost co!!on in those '@ years,

though children are being diagnosed

!ore regularly*ay be genetic

Obesity is the greatest ris" #actor #or

this disease (nd is related to increased incidence

in children

N.//* → insulin resistance in target cells

$ee decreased I cell responsiveness →

/ecreased insulin secreted by I cells

(lso abnor!al a!ount o# glucagon

secreted

These e##ects !ay be due to%

1+(bnor!ally #unctioning I cells

2+ /ecreased I cell !ass,

or a co!bination o# the two

& Target cell resistance to insulin

&+ Target cell resistance to insulin

/ue to%

/ecreased nu!ber o# insulin receptorsostreceptor events !ay be responsible

Cells Jburn outK and beco!e insensitive

Overweight, hyperlipide!ia co!!on

Abut these are precursors, notsy!pto!s)

= t i # ti

-linical manifestations

=ecurrent in#ections

Visual changes, paresthesias, #atigue

1+ 6eight loss

2+ (ppropriate diet Asee .//* above)

&+ $ul#onyl ureas

sti!ulate I cells to increase insulin

secretion

Treatment

secretion

6or"s only when I cells are still

#unctioning → (n enhance!ent o# insulinFs e##ect

at target cells

'+ E3ercise - pro!otes weight loss

-omplications of 4iabetes Mellitus (cute%

Hypoglyce!ia rapid decrease in plas!a

glucose insulin shoc"

Neurogenic responses G probably dueto decreased glucose to

hypothala!us+

$y!pto!s include%

Tachycardia, palpitations, tre!or,

pallor

Headache, di88iness, con#usion

Visual changes

Treat!ent %

provide glucose A.+V+ or subcutaneous i#

unconscious)

Observe #or relapse

Detoacidosis G involves a precipitating event%.ncreased hor!ones released wL trau!a

increased glucose produced by the bodyFs cells

This Jantagoni8esK the e##ects o# any glucose

present

.ncreased "etones in blood

(cidLbase i!balance

olyuria, dehydrationElectrolyte disturbances

Hyperventilation ADuss!aul G deep,

gasping)

CN$ e##ects (cetone on breath

Treat!ent% ‑ low dose insulin

(lso, ad!inister #luids, electrolytes

Chronic Co!plications o# /* Neuropathies nerve dys#unctions →

slowing o# nerve conduction+ .n these

patients, see%

/egeneration o# neurons

→$ensory, !otor de#icits →*uscle

atrophy, paresthesias

/epression4+.+ proble!s, as !uscle !otility

decreased

$e3ual dys#unction

*icrovascular disease G chronicdiabetes wL i!proper glucose

!etabolis! → thic"ening o# the

base!ent !e!brane o# capillaries, particularly in the eye and the "idney+

( th ill h i thi

(s the capillary changes in this way, →

/ecreased tissue per#usion

$o ische!ia → hypo3ia

.n the eye G the retina is !etabolically uite

active, so hypo3ia here is a big proble!

$o see%

=etinal ische!ia→or!ation o# !icroaneuris!s, he!orrhage,

tissue in#arct #or!ation o# new vessels

tissue in#arct, #or!ation o# new vessels,

retinal detach!ent

.n the "idney G diabetes is the !ostco!!on cause o# end stage renal‑

disease

.n5ured glo!eruliAglo!erulosclerosis)

.n these patients see%

.n these patients, see%

roteinuria Aprotein is e3creted into

the urine) → 4enerali8ed body

ede!a, hypertension

*acrovascular disease G atherosclerosislaue #or!ation increases→

.ncreased ris" o# coronary artery

disease, so increased ris" o#

!yocardial in#arction

.ncreased ris" o# congestive heart

#ailure

$tro"eeripheral vascular disease

why diabetic patients #ace

proble!s with their lower legs and#eet

.ncreased ris" o# in#ections

Endoscopic Stenting for

Pancreatic Diseases

ancreatic 2tents

• 2hape

– 9eenen * curve multiple

side holes?distal flaps

– 2herman * straight

lti l id h l

multiple side holes

proximal flap?distal

pigtail – Modified -otton*eung

stent , 2*shaped with

distal flap

• 2i3e =;B or 10 &r• ength =;BG1' cm

ancreatic 2tents , 4esign and Application-ommon !ndications

• Acute pancreatitis – 4rainage to preventpost #$- pancreatitis

:ptimal design of stents

• 2i3e 7small8• Material 7soft8

– ess irritation to ductal

– Assist endoscopictherapy

• apillotomy

• eaks

• Malignancy – 4rainage to relief pain

• -hronic pancreatitis – AdDuvant therapy for

stone and stricture

ess irritation to ductalepithelium

• Migrate outspontaneously

TechniRue of ancreatic 2tentlacement

• 4eep cannulation

with guide wireacross papilla orstricture

stricture

• V ancreatic

papillotomy• 2tent inserted

over wire andpositioned withpusher

ost*#$- ancreatitis

!ncidence

• Most commoncomplication of#$-

ossible causes

• Acinari3ation ,overfilling

• %yperosmolarity ?

• !ncidence ;*10E 1E

severe 0.1E fatal• 2ignificant medical?

social?economic andliability problem

• %yperosmolarity ?contrast allergy

• Trauma , guide wire• -oagulation inDury

• !mpaired drainage frompancreas

• acterial contamination• ile contamination

Mechanism of ost #$-ancreatitis

• apillary manipulation results in edema and sphincterspasm obstructing 4 flow leading to intracellular

activation of en3ymes

• !mproving drainage with 4 stent may prevent post#$- pancreatitis

4 2tenting revents # in2:4 ts

• >0 ts with pancreatic 2:4 after biliary #2T were

randomi3ed to 4 stent or no stent• ost #$- pancreatitis occurred in

10?=G 7'HE8 with @)o stent

– 10?=G 7'HE8 with )o stent

– 1?(1 7'.(E8 with @2tent

• ' ts 7BE8 developed # after stent removal

TarnaskyGastroenterol

4 2tenting for %igh $isk atients

• BH high*risk pts+ 2:M or difficult cannulation V #2T were

randomi3ed• ost #$- pancreatitis occurred in

– 10?=H 7'>E8 with @)o stent 7; mild ' moderate = severe8

10?=H 7'>E8 with )o stent 7; mild ' moderate = severe8

– '?=> 7;E8 with @2tent 7mild pancreatitis8

• 4 cannulation failed in '?(0 pts 7;E8

Fazel GIE 2003

!s 4 2tent )ecessary for #very#$-<

robably ):T

• !ncreased time and difficulty

• !ncreased risk

• !ncreased cost

• $isk of ductal changes from stent irritation

• )eed follow,up to insure stent migration

• May need 'nd procedure for stent removal

Jho Jill enefit from 4 2tenting<

atient &actors• 2uspected 2:4

• Zoung female

Technical &actors• 4ifficult cannulation

• re*cut sphincterotomy

• Zoung female

• rior post*#$-

pancreatitis

• )ormal serum bilirubin

re cut sphincterotomy

• ancreaticsphincterotomy

• Ampullectomy

• alloon sphincteroplasty

otential $isks of ancreatic

2tenting$isks

• &ailed stent placement

• roximal tip of stent

4ilemma

• To consider 4 stentplacement in a @high*

risk patient is a serious

damages 4

• 2tent occlusioncausing pancreatitis

• -hronic ductal

changes

• !nward stent migration

risk patient is a serious

decision

• !f successful risk of

# is reduced.

• %owever failed attempt

!)-$#A2#2 the risks

alloon 2phincteroplasty / 4ouble2tents

• 4ouble wires

• alloonsphincteroplast

•4ouble stentsfor drainage

• 4 stent for

prophylactic

drainage

ancreas 4ivisumMinor apillotomy with 4 2tenting

-hronic ancreatitis * 2tone /2tricture

#ndoTherapy for -hronicancreatitis

• ess invasive than

surgery• $esults comparable to

surgery

• 2urgery is still possibleafter failed endotherapy

• < redicts outcome

after surgery

4ilation?2tenting of ancreatic2tricture

• 9uide wire 7hydrophilic8

across stricture• 4ilators

– 9raded dilators

9raded dilators

– neumatic balloons 7(*H

• 2hort*term pancreatic

stenting to insure drainage

4ilation of Tight 4 2tricture with2oehendra 2tent $etriever

4ilation of ancreatic 2tricturevia Minor apilla

ancreatic 2tone #xtraction

• ancreatic sphincterotomy

• .0=; guide wire

• 4ilation of orifice?stricture

• 2tone extraction with wire

basket 7e.g. ''8

• < Mechanical lithotripsy

– limitations• 4 stent for drainage

• #2J to fragment large

7calcified8 stone

2ummary

• 2uccessful pancreatic stenting and drainageprevents post #$- pancreatitis

• ancreatic stenting is a useful adDunct for assisted

papillotomy

• ancreatic stenting provides drainage in patientsundergoing #2J for stone obstruction

• 2tenting helps to improve stricture post dilation and

provides short term pancreatic drainage

ancreatic )eoplasm

Types of ancreatic )eoplasms

•roadly speaking there are three basic types+

• D%ctal adenocarcinoma SG0E of pancreatic

cancers with a (E ;*year survival 7worst of any

cancer8

• *e%roendocrine t%mors aka islet*cell tumors rare• -ystic neoplasms account for N1E of pancreatic

cancers

-linical 2cenario \1 , Adenocarcinoma of the

ancreas

• Jhat are typical symptoms of pancreatic -A< – Abdominal pain*Spain can suggest neural plexus

tail lesion unresectability poor prognosis

– Anorexia

– Jeight loss – Iaundice

– ruritis *Sbiliary obstruction

– 2teatorrhea*Spancreatic duct obstruction

$isk &actors for ancreatic-ancer<

•&irmly linked to cigarette smoking

• )o clear dietary factors

• !ncreased M! associated with increased risk

• :ccupational exposures to amines 7chemistry

hairdressing rubber work8 associated with increasedrisk

Adenocarcinoma of theancreas+ -T scan

• -T can confirm pancreatic cancer with a

sensitivity of >;*G;E 7sensitivity is limited bysmaller tumor si3e8

• :ther than the presence of a pancreatic

mass what else can you determine from -T

scan< – $#2#)-# of M#TA2TA2#2 7along with -]$8

– $#2#-TA!!TZ

•Jhat makes a pancreatic mass likely resectable< – )o evidence of extrapancreatic disease

– #vidence of nonobstructive superior mesenteric*portal vein

confluence

– )o evidence of direct tumor extension to the celiac axis and

2MA – #U2 laparoscopy are universally regarded as useful

adDuncts to -T not as essential however

•@orderline $esectable lesions include+

• 2M" occlusion of a short segment 7open vein

proximally and distally8

• ody and tail lesions with V celiac para*aortic nodes

in the vicity• Tumors briefly involving the !"- may be borderline

ancreatic -ancer+ #ndoscopic AdDuncts

•#$- can be utili3ed to+ – detecting small tumors not visuali3ed on -T 7irregular

solitary duct stenoses S1cm long abrupt cutoff of main

pancreatic duct or panc and bile duct obstruction8

– palliating biliary obstruction

– brush cytology of the pancreatic duct has fair sensitivity7B0E8 but excellent specificity

• #U2 can be utili3ed to+

– aid in diagnosis and characteri3ation of lesion

– obtain tissue biopsyC may be associated with lower risk ofperitoneal seeding c?w percutaneous approach

ancreatic -ancer+ 2erum Markers

• !s there a role for serum markers< !f so what<

– -A 1G*G is a sialylated ewis A blood group antigen

commonly expressed and shed in pancreatic and

hepatobiliary disease not tumor specific

– This antigen when significantly increased can assist in

differentiating between pancreatic adenocarcinoma andinflammatory pancreatic disease

– decrease in serial -A 1G*G correlates with survival of

pancreatic patients after surgery or chemotherapy

– 4ebatable as to whether this is useful as early treatment of

recurrences have not been shown to improve outcomes

ancreatic -ancer+ )eoadDuvantTherapy

• This B0yo female has @borderline resectable

features has been stented to answer obstructive

Daundice via #$- with #U2 demonstrating a

positive adenocarcinoma

• !s there any role for neoadDuvant therapy for this

patient< !f so what sort of regimen and with what

obDectives<

!nsulinoma

• Jhipple6s Triad+• symptoms of hypoglycemia during fasting or exercise

• serum glucose N(;mg?d during symptoms

• relief of symptoms with administration of glucose

• 4efinitive test is B'*hour fast with measurement of

insulin and glucose• B;E of patients develop symptoms and 9N(0 within '( hours

• insulin+glucose ratio S0.( is indicative of insulinoma

• #levated c*peptide proinsulin levels are confirmatory

along with screening for antiinsulin antibodiessulfonylureas

%ow are insulinomas locali3ed<

• )on*invasive preoperative imaging studies fail to

locali3e =0*=;E of insulinomas

• -T?M$! etc. generally reserved by most endocrine

surgeons to r?o hepatic metastases

•!ntraoperative U?2 and palpation are the 9:4standard for finding an insulinoma GH*100E

sensitivity

Jhat is proper operation forinsulinoma<

• 9enerally wide Oocher maneuver superior and inferior

pancreatic border mobili3ation medial reflection of the

spleen• imanual palpation with U?2

• #nucleation of the lesion

uc ea o o e es o

• 2ecretin can assist in identifying pancreatic duct leak

after enucleation completed

• Jhat about lesion in pancreatic head<

• )eed to monitor glucose levels R1; minutes until lesion

METASTAT+, *E/PLASMS

• 5" times more common than primary t%mors in theliver

• via the systemic or portal veno%s circ%lation

• colon& pancreas& esophag%s& stomach&ne%roendocrine& breast& l%ng& 7idney& adrenal& ovaryand %ter%s& melanoma& and sarcomas

• Tx most R chemotherapy is the only treatment option

T]*artial %epatectomy

• most effective therapy

• minimal criteria

disease confined to the liver

disease amenable to a complete resection.

• &or small and peripherally placed lesions sublobarsegmental resections are preferred

• Anatomical segmentectomies are preferred to non*anatomical resections.

• cirrhosis constitutes the maDor obstacle to resection inpatients with %--.

• -areful patient selection

• cirrhotic patients have a late risk of death

• highly selected patients may be better treated with livertransplantation rather than resection.

Metastasis

Diret inv$,ion

L+/* node di,,e/in$tion

5-ood ,re$d

Intr$eritone$- o-oni:$tion

L+E1 -A+L1E

• Acute liver failure uncommon approx. ;000 new cases annually in

the U2.

• !n chronic liver failure * progressive hepatocyte necrosis produces afibrotic response and liver cell regeneration that leads to cirrhosis.

• Twenty*five thousand people die each year from cirrhosis making itthe eighth leading cause of death from disease in the United 2tates.

• iver stellate cells 7!to cells8 are the principal mediators of fibrosis inthe liver and are stimulated by hepatocyte necrosis and cyto7ines 7tumor necrosis factor* interleukin*1 interleukin*H8 gro4thfactors 7epidermal growth factor platelet*derived growth factor

transforming growth factor 18 released by platelets and Oupfferand endothelial cells.

iver &ailure

Mackay Memorial %ospital

4epartment of !nternal Medicine

4ivision of 9astroenterology

$(陳泓達

BJ9J!!

athology• SG0 adenocarcinoma+ three types

2clerosing 7scirrous8

• !ntense desmoplastic reaction• &ibrosis makes diagnosis more difficult

• !nvade bile duct walls with reduced surgical options and cure

• eads to as @2-*like appearance on #$-

• Most are of this type

)odular • Annular lesion

• resent at advanced stage

apillary

• ulky mass in -4

• est resectability

-linical Manifestation and 4iagnosis

• ruritis+ HHE

• Abdominal pain+ =0*;0E

• Jeight loss+ =0*;0E

&e er p to '0E

• &ever+ up to '0E

• ain+ @dull ache $U• Iaundice+ G0E

• %epatomegaly+ ';*(0E

• $U mass+ 10E

-linical Manifestation and 4iagnosis

• ruritis+ HHE• Abdominal pain+ =0*

• Iaundice+ G0E• %epatomegaly+

'; (0E

• Jeight loss+ =0*;0E• &ever+ up to '0E

• ain+ @dull ache

';*(0E

• $U mass+

Tumor Markers<

• ,EA val%e R !.5 W sensitivity $BC& specificity

• ,A #J(J+ varies results*sensitivity ;=E through >GE

• $esults may be related to cut*off value

$esults may be related to cut*off value

• -holestasis and cholangitis also play a role• 6oth ,EA and ,A(#J(J 2,A(#J(J G X,EA x >"Y3

$adiology

Ultrasound

• -an detect vascular invasion

-omputer tomography

• ile ducts and nodal involvement

• Multiphasic

-holangiography

• rush cytology and bile sampling• Therapeutic

TreatmentSurgical

• 4istal disease highest resectability

• G0E resectability rate

• -riteria

Absence of lymph nodes or distant liver metastases

Absence of vascular 7portal vein or hepatic artery8 invasion

Absence of extrahepatic adDacent organ invasion

Absence of disseminated disease

• :perate with bilirubin N = mg?dl

• Jhipple procedure for distal disease

Treatment Ad4u.ant

• $adiotherapy

• $adiation plus chemotherapy

• AdDuvant chemotherapy

• )eoadDuvant chemotherapy

TreatmentPalliati.e

• 2urgical bypass vs stenting

• Metal stents associated with longer patency rates

• lastic suited for patients with shorter survival

• *o increase in s%rvival

-hemotherapy

• ;*&U based therapy• 9emcitabine

• -apecitabine• )exavar

iver Transplantation<

ile Acid metabolism

• iver involved in synthesis and excretion

• ile acids synthesi3ed from cholesterol

• %ydrophobic and hydrophilic properties

• Act as detergents

Act as detergents

• &orm micelles to for lipid absorption• rimary secondary and tertiary bile acids

ile Acid metabolism

• #nterohepatic circulation

• secretion rate of bile acids greater than pools

• small amounts lost in stool made up by synthesis

• bile acids reabsorbed in terminal ileum

• G;*G>E reabsorbed serum levels are low

• bile acids may be deconDugated by bacteria

• deconDugated absorbed rapidly by diffusion

4isorders of bile acid metabolism

• :bstructed or diseased secretory system• 4efective synthesis of bile acids

• acterial overgrowth in small intestine

! d l f bil id i l

• !ncreased loss of bile acids in stool

– compensated

– decompensated

ile Acid metabolism in liver disease

• 4ecreased hepatic synthesis uptake transport

• %epatocellular diseases have decreased+

*uptake synthesis and conDugation

• iliary diseases may also have decreased+

*secretion into bile ducts

• %igh plasma bile acids levels may result

• 4ecreased enterohepatic circulation

• "ery high levels in cholestatic diseases

Adult -holestatic iver 4isease – -

– 2-

– !ntrahepatic cholestasis

– 9"%4 liver

– T) induced cholestasis

– 2arcoidosis

– idipathic ductopenia

– iver transplant reDection

– -ystic fibrosis

– A!42 cholangiopathy

4rug induced cholestasis

• Anabolic steroids• :ral

contraceptives

• -yclosporine

• Antibiotics

• )euroleptics

ediatric cholestatic diseases

• -ystic fibrosis• Alagille6s syndrome

•iliary atresia

• yler6s disease

• !nborn errors of

metabolism

iver disease in cholestasis

• Mediated by high levels of toxic bile acids

• referential retention of hydrophobic bile acids

• 4irect damage to hepatocytes and bile duct cells

• ithocholic and chenodeoxycholic acids are toxic

• 4egree of liver damage related to bile acid level

4egree of liver damage related to bile acid level

• 4amage to cell membranes necrosis• -holestasis may lead to immune activation

iver disease in cholestasis

• Mechanism is probably multifactorial

• !nitial immunologic insult

• ile duct loss and failure to transport bile acids

• $etention of hydrophobic bile acids

• -holate chenodeoxycholate accumulate

• further direct and immune*mediated damage

-linical complications of cholestasis

• ruritus very common and may be disabling

• #xact mechanism unknown• ossible relationship with bile acid levels

• &at malabsorption and steatorrhea

• &at soluble vitamin deficiencies 7A 4 # O8

• &at*soluble vitamin deficiencies 7A 4 # O8

• Marked elevation in cholesterol levels

• ]anthomas and xantholesmas

• #arly and severe osteoporosis may occur

aboratory tests in cholestaticdisease

• "ery high serum alkaline phosphatase 99T

• ess striking elevation in other liver en3ymes

• 2erum bilirubin is elevated late in the disease

• &our stages of disease+

– one+ no symptoms

– two+ fatigue and pruritus

– three+ liver fibrosis and elevated bilirubin

– four+ cirrhosis and liver failure

• 4ifferential diagnosis –

2arcoidosis – 9ranulamatous hepatitis

– %epatitis -

– 4rug induced hepatitis

4rug induced hepatitis

– 2- – Alcoholic liver disease

– !diopathic adult onset ductopenia

– Autoimmune hepatitis

#pidemiology of -

• $ochester M) #pidemiology roDect

• !ncidence and prevalence of -

• Age adDusted incidence '.B?100000 – (.; per 100000 7women8

– 0.B per 100000 7men8

• Age and sex adDusted prevalence (0.'?100000 – H;.( per 100000 7women8

– 1'.1 per 100000 7men8

Kim et al., Gastroenterology 2000;119:1631-6

&eatures of -

• -linical &eatures

• 2icca syndrome ;0E• Thyroid disease 1;E

• Arthritis 10E

• ess -ommon N;E

• aboratory

features• AMA positive 7G;E8

• ess -ommon N;E

– $aynaud6s – reast cancer

– 2cleroderma

– $enal stones

• A)A positive• A2MA positive

• #levated cholesterol

• #levated !gM level

2ymptoms and 2igns of -

• &atigue H;E

• Ascites1E

• ruritus ;;E

• Iaundice 1HE

• leeding =E

•#ncephalopathy 'E• Asymptomatic '0E

'i,to-oi St$in of P5C

From Diseases of the i!er, "#hiff $%

PSCPSC

M$-e, (2>8)

Intr$ 1E3tr$*e$ti

ile 4uct 4iseases

P5CP5C

Fe/$-e, (>8)

Inter-o&u-$r

Pou-$tion

5i-e Dut,

A&nor/$-

Nor/$-ERCP

UC A,,oi$tion

C*o-$nio CA Ri,6

Co/-i$tion,

athogenesis of 2-

• acterial translocation to biliary tree

– Animal model of bacterial overgrowth – ink with ulcerative colitis

• !mmunologically mediated – -# in bile

– %A associations

• 4eficient biliary chloride transport – -&T$ mutations

Treatment of cholestatic diseases

• )onspecific and specific

• -holestyramine and anti*pruritic therapies

• "itamin supplementation

• )utritional support

• U4-A reasonable in all cholestatic diseases• !mmunosuppressants

• Antifibrotics

ossible mechanisms of U4-A

• %epatoprotective

• -ytoprotective

• #ffect on biliary transport

• !mmunomodulatory

roperties of U4-A

• %epatoprotective*displace hydrophobic acids

*prevent liver damage by hydrophobic acids

*< block dissolution of membrane*bound lipids

< block dissolution of membrane bound lipids

*mdr' knockout mouse model

*after H months 10*1' mg?kg?day U4-A is

;0*H0E of bile acid pool

roperties of U4-A

• U4-A effect on biliary transport

*increased secretion of bile acids by ducts* 4ecreased -4-A levels in - patients

*!ncreased secretion of phospholipids

* ilirubin reduction may be due to increased

ilirubin reduction may be due to increased

biliary transport*decreased acidity of bile

* increased bile flow

!mmunomodulatory

• Abnormal %A antigens on cells in cholestasis• May lead to immune activated damage

• Treatment with U4-A reduces %A expression

• Unknown whether this is primary or secondary

Unknown whether this is primary or secondary

• May be maDor beneficial effect in -

-onditions treated with U4-A• Primary biliary cirrhosis

• Primary sclerosing cholangitis

• +ntrahepatic cholestasis of pregnancy• ;raft vers%s host disease of the liver

• ,ystic fibrosis liver disease

• TP*(related cholestasis

• Liver graft re8ection• *onalcoholic steatohepatitis

• eno(occl%sive disease of the liver

• ,ardiac graft re8ection

• 4oses of 10*1; mg?kg?day studied

• -ombined analysis of three studies• :ver ;00 patients treated

• Median follow up ( years

• 2urvival free of transplantation improved

2urvival free of transplantation improved

• ='E reduction in death or transplantation

• enefit greatest with elevated bilirubin

• U2 multicenter also showed survival benefit

U4-A 7rsodeoxycholic acid3 in-

• May delay onset of esophageal varices

• !mprovement in pruritus variable

• Ten year survival without :T improved

• 4ecrease in @florid bile duct lesions

• !mproved inflammation and necrosis• ossible stabili3ation of fibrosis

• U4-A is cost effective therapy

%igh 4ose U4-A for 2-

• $andomi3ed trial in 'H patients with 2-

• '0 mg?kg U4-A vs placebo for ' years• '' patients had repeat #$- and biopsy

• #valuation every = months

• )o change in symptoms with U4-A

• !ncreased total serum bile acids

• 2aturation with U4-A S B0E

2ignificantly improved+• 2erum A

• 2erum 99T

• -holangiograms

'i* Do,e UDCA for PSC

• -holangiograms

• &ibrosis grade

(it#hell et al., Gastroenterology 2001;121:900-90)

#ffect of U4-A on histology

• iopsy done before and after (years

• &lorid bile duct lesions

• 9ranulomas

• obular inflammation

• obular necrosis Degott et al.,*e+atology 1999;29:100)-12

#ffect of U4-A on survival

• (0 symptomatic patients treated 10 years

• ' stopped early for worsened symptoms

• oth alive ( years later

• => treated for up to 10 years

• 2urvival benefit for 2tage ! disease• Trend for improved survival in !!*!"

• 2ymptoms improved but recurred in ;0E

ateson an& Ge&ling, ostgra&ate (e& / 199;):2-

2erum bilirubin during U4-A

• 2urvival with U4-A vs placebo

• 4atabase of ;(> patients studied

• 2urvival after normali3ation of bilirubin

• Transplant*free survival improved 7$$ =.B8

2i il t l bili bi l b

• 2imilar to normal bilirubin placebo group

• ilirubin predicted death :T in both

• biliS =0µmol?l+ $$ of death :T 7H ;.B8

onnan& et al., *e+atology 1999;29:39-3

#ffect of U4-A on histology

• )o change in ductular proliferation• )o change in ductopenia

• )o change in piecemeal necrosis

• &ibrosis worse in 1' stable in =0

• rogression related to

necroinflammation Degott et al.,*e+atology 1999;29:100)-12

#ffect of U4-A on fibrosis

• $ate early to late stage• 1H' paired liver biopsies

• ; ] lower rate from early

to late stage

• Maintained lower stage

• )o regression seen

7=E per yr8

or+e#hot *e+atology 2000;32:1196-9

ong*term effects of U4-A

• 10 year survival examined

• )eed for :T risk of death

• ''; patients treated U4-A 1=*1; mg?kg

• )o control group

• #xpected survival using Mayo model• 2urvival better than predicted

• ower than general &rench population

• -omparable in patients without cirrhosis o+on *e+atology 29:166-)1

#ffect of U4-A on varices

• 1>0 patients incontrolled trial

• #ndoscopyperformed every twoyears

P#.##8

• 1=G had no variceson entry

• ower incidence ofvarices with U4-Aafter ( years

in&or et al., (ayo lin ro# 199);)2:113)-0

ong*term U4-A therapy

• 1G' randomi3ed to U4-A versus placebo

• 4ecreased liver en3ymes with U4-A• Apparent after = months of therapy

• 4eath or transplant defined failure

• )o difference in time to failure

)o difference in time to failure

• U4-A improved portal inflammation

• U4-A slowed histologic stage progression

ares / *e+atol 2000;32:61-6

U4-A effect on histology

• U2 ' year

multicenter trial

• U4-A versus

placebo

• revalence of floridduct lesions

decreased

• More common with

early stage disease

om4es *e+atology 1999;30:602-

Jhich patients respond to U4-A<

• B0 patients treated 10*1; mg?kg H*1= years

• ==E with 2tage ! or !! had normal &T• %istology improved

• HBE without normal &T

• %istology was not improved to same degree

gy p g

• !ncomplete responders had higher alkalinephosphatase 99T

• A S H00 99TS1=1

es#hner Gt 2000;6:121-6

2ummary

• -holestatic liver diseases common

• $ecogni3e associated complications

• U4-A accepted therapy in -

• ong*term improvement in responders

• :ngoing studies in 2-

Cirr*o,i, of t*e Liver

4escription

• A chronic progressive disease of the liver

– #xtensive parenchymal cell

degeneration – 4estruction of parenchymal cells

4escription

• $egenerative process is disorgani3ed resulting in

abnormal blood vessel and bile duct relationships

from fibrosis

4escription

•)ormal lobular structure distorted by fibroticconnective tissue

• obules are irregular in si3e and shape with impairedvascular flow

• !nsidious prolonged course

• -ell necrosis occurs• 4estroyed liver cells are replaced by scar tissue

• )ormal architecture becomes nodular

• &our types of cirrhosis+

– Alcoholic 7aennec6s8 cirrhosis – ostnecrotic cirrhosis

– iliary cirrhosis

– -ardiac cirrhosis

#xactly %ow Much 4o Zou 4rink<

• #stimated that the development of cirrhosis reRuires

on average the ingestion of >0 grams of ethanoldaily for 10 to '0 years

• This corresponds to approximately one liter of wine

eight standard si3ed beers or one half pint of hard

liRuor each day

• Alcoholic 7aennec6s8 -irrhosis

– Associated with alcohol abuse

– receded by a theoretically reversible fatty infiltration of the

liver cells

– Jidespread scar formation

• ostnecrotic -irrhosis

– -omplication of toxic or viral hepatitis

– Accounts for '0E of the cases of cirrhosis

– road bands of scar tissue form within the liver

iliary -irrhosis – Associated with chronic biliary obstruction and infection

– Accounts for 1;E of all cases of cirrhosis

• -ardiac -irrhosis – $esults from longstanding severe right*sided heart failure

Manifestations of iver -irrhosis

Fi. "!2

-linical Manifestations#arly Manifestations

• :nset usually insidious

• 9! disturbances+

– Anorexia

– 4yspepsia

– &latulence

atu e ce

– )*" change in bowel habits

-linical Manifestations#arly Manifestations

• Abdominal pain• &ever

• assitude

• Jeight loss

• #nlarged liver or spleen

-linical Manifestationsate Manifestations

• Two causative mechanisms

– %epatocellular failure

– ortal hypertension

-linical ManifestationsIaundice

• :ccurs because of insufficient conDugation of bilirubin

by the liver cells and local obstruction of biliary ducts

by scarring and regenerating tissue

-linical ManifestationsIaundice

• !ntermittent Daundice is characteristic of biliary

cirrhosis

• ate stages of cirrhosis the patient will usually be

Daundiced

-linical Manifestations2kin

• 2pider angiomas 7telangiectasia spider nevi8

• almar erythema

-linical Manifestations #ndocrine 4isturbances

• 2teroid hormones of the adrenal cortex 7aldosterone8

testes and ovaries are metaboli3ed and inactivated

by the normal liver

-linical Manifestations #ndocrine 4isturbances

• Alteration in hair distribution

– 4ecreased amount of pubic hair

– Axillary and pectoral alopecia

-linical Manifestations %ematologic 4isorders

• leeding tendencies as a result of decreased

production of hepatic clotting factors 7!! "!! !] and

-linical Manifestations %ematologic 4isorders

• Anemia leukopenia and thrombocytopenia are

believed to be result of hypersplenism

-linical Manifestations eripheral )europathy

• 4ietary deficiencies of thiamine folic acid and

vitamin 1'

-omplications

• ortal hypertension and esophageal varices

• eripheral edema and ascites

• %epatic encephalopathy

• &etor hepaticus

-omplications ortal %ypertension

• -haracteri3ed by+ – !ncreased venous pressure in portal circulation

– 2plenomegaly

– #sophageal varices

– 2ystemic hypertension

• rimary mechanism is the increased resistance to

blood flow through the liver

-omplications

ortal %ypertension

Esophageal Varices

F !ncreased blood flow through the

portal system results in dilation

and enlargement of the plexus

veins of the esophagus and

produces varices

Esophageal Varices

F "arices have fragile vessel walls

which bleed easily

Internal Hemorrhoids

F :ccurs because of the dilation of the

mesenteric veins and rectal veins

Caput Medusae

F -ollateral circulation involves the superficial veins of the

abdominal wall leading to the development of dilated veins

around the umbilicus

-omplications eripheral #dema and Ascites

F Ascites+

** !ntraperitoneal accumulation of

watery fluid containing small

amounts of protein

-omplications eripheral #dema and Ascites

F &actors involved in the pathogenesis of ascites+

* %ypoalbuminemia

−↑ evels of aldosterone

−↑ ortal hypertension

-omplications

• iver damage causes blood to enter systemic

circulation without liver detoxification

-omplications %epatic #ncephalopathy

• Main pathogenic toxin is )%= although other

etiological factors have been identified

• &reRuently a terminal complication

-omplications&etor %epaticus

• Musty sweetish odor detected on the patient6s breath

• &rom accumulation of digested by*products

4evelopment of Ascites

Fi. "!9

4iagnostic 2tudies

• iver function tests

• iver biopsy

• iver scan

• iver ultrasound

4iagnostic 2tudies

• #sophagogastroduodenoscopy

• rothrombin time

• Testing of stool for occult blood

-ollaborative -are

• $est

• Avoidance of alcohol and anticoagulants

• Management of ascites

-ollaborative -are

• revention and management of esophageal varicealbleeding

• Management of encephalopathy

-ollaborative -are Ascites

• %igh carbohydrate low protein low )aV diet

• 4iuretics

• aracentesis

• eritoneovenous shunt

– rovides for continuous reinfusion of ascitic fluid from the

abdomen to the vena cava

eritoneovenous 2hunt

Fi. "!

-ollaborative -are Esophageal Varices

• Avoid alcohol aspirin and irritating foods

• !f bleeding occurs stabili3e patient and manage the

airway administer vasopressin 7itressin8

• #ndoscopic sclerotherapy or ligation

• alloon tamponade

• 2urgical shunting procedures 7e.g. portacaval shunt

2engstaken*lakemore Tube

Fi. "!

ortosystemic 2hunts

Fi. "!88

-ollaborative -are Hepatic Encephalopathy

• 9oal+ reduce )%= formation – rotein restriction 70*(0g?day8

– 2terili3ation of 9! tract with antibiotics 7e.g. neomycin8

– lactulose 7-ephulac8 , traps )%= in gut

– levodopa

4rug Therapy

• There is no specific drug therapy for cirrhosis

• 4rugs are used to treat symptoms and complications of

advanced liver disease

)utritional Therapy

• 4iet for patient without complications+

– %igh in calories – ↑ -%:

– Moderate to low fat

– Amount of protein varies with degree of liver damage

)utritional Therapy

• atient with hepatic encephalopathy

– "ery low to no*protein diet

• ow sodium diet for patient with ascites and edema

)ursing Management)ursing Assessment

• ast health history

• Medications

• -hronic alcoholism

J i ht l

• Jeight loss

)ursing Management)ursing 4iagnoses

• !mbalanced nutrition+ less than body reRuirements

• !mpaired skin integrity

• !neffective breathing pattern

• $isk for inDury

$isk for inDury

)ursing Managementlanning

• :verall goals+

– $elief of discomfort

– Minimal to no complications

– $eturn to as normal a lifestyle as possible

)ursing Management)ursing !mplementation

• %ealth romotion

– Treat alcoholism

– !dentify hepatitis early and treat

– !dentify biliary disease early and treat

• Acute !ntervention – $est

– #dema and ascites

– aracentesis

– 2kin care

– 4yspnea

4yspnea – )utrition

• Acute !ntervention – leeding problems

– alloon tamponade

– Altered body image

– %epatic encephalopathy

• Ambulatory and %ome -are

– 2ymptoms of complications

– Jhen to seek medical attention

– $emission maintenance

– Abstinence from alcohol

)ursing Management#valuation

• Maintenance of normal body weight

• Maintenance of skin integrity

• #ffective breathing pattern

• )o inDury

• )o signs of infection

)o signs of infection

iver -irrhosis

O. 4ionne osey M4 M%/

O. 4ionne osey M4 M%!nternal Medicine / ediatrics 4ecember G

%istopathology

Morphologic -lassification

• $elatively nonspecific with regard to etiology

• The morphologic appearance of the liver may changeas the liver disease progresses

– micronodular cirrhosis usually progresses to macronodular

cirrhosis

• 2erological markers available today are more specificthan morphological appearance of the liver for

2erological markers available today are more specificthan morphological appearance of the liver for

determining the etiology of cirrhosis

• Accurate assessment of liver morphology may only

be achieved at surgery laparoscopy or autopsy

#valuation of -irrhosis

-omplications

• Ascites

• 2pontaneous acterial eritonitis• %epatorenal syndrome

• "ariceal hemorrhage

• %epatopulmonary syndrome

-omplications

• :ther ulmonary syndromes

– %epatic hydrothorax – ortopulmonary %T)

• %epatic #ncephalopathy

• %epatocellular carcinoma

Ascites

• Accumulation of fluid within the peritoneal cavity

• Most common complication of cirrhosis• Two*year survival of patients with ascites is

approximately ;0 percent

Ascites

• Assessment of ascites

– 9rading• 9rade 1 ^ mildC 4etectable only by U2

• 9rade ' ^ moderateC Moderate symmetrical distension of theabdomen

• 9rade = ^ large or gross asites with marked abdominal

distension

– :lder system *subDective• 1V minimal barely detectable

• 'V moderate

• =V massive not tense

• (Vmassive and tense

Ascites

• !maging studies for confirmation of ascites

– Ultrasound is probably the most cost*effective modality

Ascites

Jho gets a belly tap<

Jhat do ! want to order <

Ascites

• Treatment aimed at the underlying cause of the

hepatic disease and at the ascitic fluid itself • 4ietary sodium restriction

– imiting sodium intake to >> meR 7'000 mg8 per day

Ascites

• The most successful therapeutic regimen is the

combination of single morning oral doses of2pironolactone and &urosemide beginning with 100mg and (0 mg

• Two maDor concerns with diuretic therapy for cirrhoticascites+

– :verly rapid removal of fluid i l t l t i b l

– rogressive electrolyte imbalance

2pontaneous acterial eritonitis

• !nfection of ascitic fluid

• Almost always seen in the setting of end*stage liverdisease

• The diagnosis is established by

– A positive ascitic fluid bacterial culture

– #levated ascitic fluid absolute polymorphonuclear leukocyte7M)8 count 7 S';0 cells?mm=8

7M)8 count 7 S';0 cells?mm=8

2pontaneous acterial eritonitis

– &ever – Abdominal pain

– Abdominal tenderness

– Altered mental status

%epatorenal syndrome

• acute renal failure coupled with advanced

hepatic disease 7due to cirrhosis or less oftenmetastatic tumor or severe alcoholic hepatitis8

• characteri3ed by+

– :liguria

– benign urine sediment

– very low rate of sodium excretion

– progressive rise in the plasma creatinine

concentration

%epatorenal 2yndrome

• $eduction in 9&$ often clinically masked

• rognosis is poor unless hepatic function improves• )ephrotoxic agents and overdiuresis can precipitate

"ariceal hemorrhage

• :ccurs in '; to (0 percent of patients with cirrhosis

• rophylactic measures• 2creening #94 recommended for all cirrhotic

patients

%epatopulmonary syndrome

• %epatopulmonary syndrome

– iver disease – !ncreased alveolar*arterial gradient while breathing room air

– #vidence for intrapulmonary vascular abnormalities referred

to as intrapulmonary vascular dilatations 7!"4s8

%epatic %ydrothorax

• leural effusion in a patient with cirrhosis and

no evidence of underlying cardiopulmonarydisease

• Movement of ascitic fluid into the pleural

space through defects in the diaphragm and

is usually right*sided

• 4iagnosis *pleural fluid analysis

– reveals a transudative fluid

– serum to fluid albumin gradient greater than 1.1

%epatic hydrothorax

• -onfirmatory study+

– 2cintigraphic studies demonstrate tracer in the chest cavityafter inDection into the peritoneal cavity

• Treatment options+

– diuretic therapy

– periodic thoracentesis

– T!2

ortopulmonary %T)

• $efers to the presence of pulmonary hypertension in

the coexistent portal hypertension• revalence in cirrhotic patients is approximately 'percent

• 4iagnosis+ – 2uggested by echocardiography

– -onfirmed by right heart catheteri3ation

• 2pectrum of potentially reversible neuropsychiatric

abnormalities seen in patients with liver dysfunction – 4iurnal sleep pattern pertubation

– Asterixis

– %yperactive deep tendon reflexes

– Transient decerebrate posturing

• Monitoring for events likely to precipitate %# _i.#.*

variceal bleeding infection 7such as 28the administration of sedatives hypokalemia

and hyponatremia`

• $eduction of ammoniagenic substrates

– actulose ? lactitol

4i t t i ti f t i

– 4ietary restriction of protein

– inc and melatonin

%epatocellular -arcinoma

• atients with cirrhosis have a markedly increased risk

of developing hepatocellular carcinoma• !ncidence in well compensated cirrhosis is

approximately = percent per year

rognostic Tools

• M#4 7model for end*stage liver disease8

– !dentify patients whose predicted survival post*procedurewould be three months or less

• M#4 K =.>_serum bilirubin 7mg?d8` V 11.'_!)$` V

G.H_serum creatinine 7mg?d8` V H.(

rognostic Tools

• -hild*Turcotte*ugh 7-T8 score

– initially designed to stratify the risk of portacaval shuntsurgery in cirrhotic patients

– based upon five parameters+ serum bilirubin serum albumin

prothrombin time ascites and encephalopathy

– good predictor of outcome in patients with complications of

portal hypertension

rognostic Tools

• AA-%# !!! 7acute physiology and chronic health

evaluation system8 – 4esigned to predict an individual5s risk of dying in the hospital

Treatment :ptions

• The maDor goals of treating the cirrhotic patient

include+ – 2lowing or reversing the progression of liver disease

– reventing superimposed insults to the liver

– reventing and treating the complications

– 4etermining the appropriateness and optimal timing for liver

transplantation

iver Transplantation

• iver transplantation is the definitive treatment for

patients with decompensated cirrhosis• 4epends upon the severity of disease Ruality of life

and the absence of contraindications

iver Transplantation

• Minimal criteria for listing cirrhotic patients on the liver

transplantation list include – A child*ugh score B

– ess than G0 percent chance of surviving one year without a

transplant

– An episode of gastrointestinal hemorrhage related to portal

hypertension– An episode of spontaneous bacterial peritonitis

An episode of spontaneous bacterial peritonitis

"accinations

• %epatitis A and • neumococcal vaccine

• !nfluen3a vaccination

2urveillance

• 2creening recommendations+

– serum A& determinations and ultrasonography every sixmonths

Avoidance of 2uperimposed !nsults

• Avoidance of+ – Alcohol

– Acetaminophen

– %erbal medications

-ollaborative -are

• $est

• Avoidance of alcohol and anticoagulants

• Management of ascites

-ollaborative -are

• revention and management of esophageal varicealbleeding

• Management of encephalopathy

• %igh carbohydrate low protein low )aV diet

• 4iuretics

• aracentesis

• eritoneovenous shunt – rovides for continuous reinfusion of ascitic fluid from the

abdomen to the vena cava

• Avoid alcohol aspirin and irritating foods

• !f bleeding occurs stabili3e patient and manage the

airway administer vasopressin 7itressin8

• #ndoscopic sclerotherapy or ligation

• alloon tamponade

• 2urgical shunting procedures 7e.g. portacaval shunt

Peritoneoveno%s Sh%nt

2engstaken*lakemore Tube

ortosystemic 2hunts

4rug Therapy

• There is no specific drug therapy for cirrhosis• 4rugs are used to treat symptoms and complications of

advanced liver disease

)utritional Therapy

• 4iet for patient without complications+

– %igh in calories – ↑ -%:

– Moderate to low fat

– Amount of protein varies with degree of liver damage

)utritional Therapy

• atient with hepatic encephalopathy – "ery low to no*protein diet

• ow sodium diet for patient with ascites and edema

)ursing Management)ursing Assessment

• ast health history

• Medications

• -hronic alcoholism

• Jeight loss

)ursing Management)ursing 4iagnoses

• !mbalanced nutrition+ less than body reRuirements

• !mpaired skin integrity

• !neffective breathing pattern

• $isk for inDury

)ursing Managementlanning

• :verall goals+ – $elief of discomfort

– Minimal to no complications

– $eturn to as normal a lifestyle as possible

• %ealth romotion – Treat alcoholism

– !dentify hepatitis early and treat

– !dentify biliary disease early and treat

• Acute !ntervention

– $est – #dema and ascites

– aracentesis

– 2kin care

– 4yspnea

– )utrition

)ursing Management

)ursing !mplementation

• Acute !ntervention

– leeding problems

– alloon tamponade

– Altered body image

– %epatic encephalopathy

)ursing Management

)ursing !mplementation

• Ambulatory and %ome -are

– 2ymptoms of complications

– Jhen to seek medical attention

– $emission maintenance

– Abstinence from alcohol

)ursing Management

#valuation

• Maintenance of normal body weight

• Maintenance of skin integrity

• #ffective breathing pattern

• )o inDury

• )o signs of infection

4iseases of the iver / iliary Tract

• The circulation of blood through the intestines / liver is uniRue in humananatomy+ blood from one capillary system the intestinal flows into anothercapillary system the hepatic before returning to the heart

#nterohepatic -irculation

MaDor 4eterminants of 4isease• The metabolic conseRuences of liver disease are serious/ include – toxic accumulations of

• metabolic waste 7especially ammonia / bilirubin8

• drugs / toxins• endogenous hormones 7especially estrogen8

– bleeding associated with a deficiency of coagulation factors – edema associated with a deficiency of albumin – failure to absorb intestinal fat because of a deficiency of bile

• "iral hepatitis is a common contagious disease• -irrhosis is the final endpoint for many liver diseases

y• ortal %T) is the most important conseRuence of

cirrhosis / can be associated with liver failure / severehemorrhage

• 2tones often form in the gallbladder / may pass into /obstruct the bile duct

$esponse to !nDury

• $esponds well as it has a functional reserve that mustsuffer a large loss before become symptomatic

• iver function tests 7&Ts8 – en3ymes

• actic dehydrogenase 74%8

• Aspartate aminotransferase 7A2T8

• Alanine aminotransferase 7AT8

• Alkaline phosphatase 7AO8 – bilirubin

– albumin

albumin

– T / TT

– viral antigens / antibodies

– autoimmune antibodies

Anatomic atterns of !nDury

• !nflammation

– hepatitis• 4egeneration

– hydropic

– fatty

• )ecrosis – infarct

-ouncilman bodies

– -ouncilman bodies

• &ibrosis

– cirrhosis

&unctional atterns of iver !nDury• 4irect metabolic

conseRuences

– Daundice – cholestasis

• accumulation of bile

acids / cholesterol in

blood due to

obstruction

– hepatic failure

hepatic failure

Iaundice

• ilirubin S 'mg?dl

-holestasis

• Usually accompanied by Daundice / pruritis

• 4ue to – primary liver disease

– drug interference with bile secretion

– pregnancy

• #levated blood cholesterol• ]anthomas

• !ncreased AO

%epatic &ailure

• 4ie within a few weeks or months• May be sudden inDury or chronic inDury•

oss of G0E of function• -linically – Daundice – ascites – fetor hepaticus – hypoalbuminemia – hypoglycemia

– palmar erythema – spider angiomata – testicular atrophy– balding

balding – gynecomastia – bleeding disorders – hepatorenal syndrome

– hepatic encephalopathy

-irrhosis

• &inal common end*

stage for a variety of

chronic liver diseases

• atterned fibrosischaracteri3ed byinterconnecting bandsof scar tissue

– divides liver into smallnodules separated bydense fibrous tissue

• rogressive

• !rreversible

• !ncurable

Anatomic Types of -irrhosis• ortal – caused by diffuse liver cell

inDury – repeated episodes of necrosis

followed by regeneration /

growth of fibrous tissue fromportal triad area – most common type – usually due to alcoholic liver

disease or chronic viralhepatits

• iliary – caused by chronic disease of

the biliary tree– chronic inflammation of bile

chronic inflammation of bileducts due to

• autoimmune disease• obstruction by gallstones

• sclerosing cholangitis

• -auses portal hypertension

"iral %epatitis

• 2everal viruses involved

– %A"

– %"

– %-"

– %4"

– %#"

• %epatitis A is a mild epidemic disease spread bycontaminated food / % :

contaminated food / %': – does not cause chronic hepatitis or cirrhosis

• %epatitis / - are spread from individual to individualby needles or sexual contact – can cause chronic hepatitis or cirrhosis

-linical 2yndromes of "iral

%epatitis• Asymptomatic hepatitis

– no lasting liver inDury

• -arrier state – harbors virus but is asymptomatic

– can transmit to others

– mostly %-"

• Acute viral hepatitis

– ( clinical phases

• -hronic viral hepatitis

• &ulminant hepatic failure

• %epatocellular carcinoma – increased risk with %" / %-"

Acute "iral %epatitis

• !ncubation

– a few weeks

• 2ymptomatic

preDaundice phase

– malaise

– fatigue

– nausea?vomiting

– anorexia

$U pain

• 2ymptomatic Daundice

– Daundice appears / other

symptoms fade

– increase in conDugated

bilirubin

– pale stools• -onvalescence

Daundice fades

– $U pain

– fever

– headache

– Daundice fades

– infectivity disappears

– Abs in blood

-hronic "iral %epatitis

• iver biopsy / H months or more of clinical or labevidence

• About 10E of %" patients / ;0E of %-" patients• ab tests reveal extent of disease as there are few

signs?symptoms – prolonged T / TT – increased en3ymes

– increased bilirubin• resent with

– hepatomegaly

– splenomegaly – palmar erythema

– spider angiomas

&ulminant %epatic &ailure

• Acute liver disease that progresses to hepatic failure orencephalopathy in Dust a few weeks

• More than of the cases are fulminant hepatitis usually involving%A" or %"

• :ther causes include drugs heat stroke

%epatitis A• %A"

• #pidemic hepatitis

•rimarily fecal*oral transmission• enign / self*limiting

• !ncubation is about '*H weeks

• Most common type in the world – infection more common than the disease

– more common in developing nations

– about 10000 new cases?yr in U2

• &atalities rare

• )o carrier state

• "accine

%epatitis

• %"

• !nfects hundreds of millions worldwide

• !ncubation varies from a few weeks to H months

Acute !nfection• 4etected by presence of hepatitis surface antigen 7%sAg8• "iremia may last for many weeks• 1st antibody to appear is hepatitis core antigen antibody 7anti*%c8• eginning of recovery marked by appearance of hepatitis surface

antigen antibodies 7anti*%s8

– confers immunity

• Transmitted in – blood

– saliva

– semen

– almost any bodily fluid

• 2pread by – sexual contact

– blood transfusion

– renal dialysis

– needlestick – !" drug users

– fetus in utero or duringvaginal delivery

– 1?= of cases notknown

%epatitis -

• MaDor cause of chronic liver disease

• !ncubation varies from a few weeks to H months

• About (0000 new cases?yr

• About 'E have antibodies indicating previous infection

• About ;0E of these have detectable virus in blood

– indicates a chronic carrier state

• Transmission – over 1'? of new infections due to !" drug abuse

– about 1;E through sexual contact infected health care workers/ neonates

– in about 1?= of cases not known

• Mutating $)A virus with do3ens of subtypes has madedeveloping a vaccine difficult

• %epatitis 4 – %4"

– delta virus

– co*exist with %"

• co*infect• infect a carrier of %"

– mostly in• !" drug abusers

• hemophiliacs

• %epatitis # – rare in U2 but most

common form ofepidemic hepatitis in!ndia

– transmitted like %A"

– mild / self*limiting

Anatomic athology of %epatitis• -arrier state

– liver biopsy normal usually

– in %-" may have evidence

of low*grade inflammation – in %" may have @ground

glass appearance due to

virus particles

• Acute hepatitis

– hydropic degeneration

– chronic inflammation

necrosis of individual cells

• &ulminant hepatitis or

hepatic failure

– extensive necrosis

• -hronic hepatitis – see those changes seen in

acute but more severe

damage

– disorgani3ed

– more intense inflammatory

reaction

more extensive necrosis

– necrosis of individual cells – more extensive necrosis

– scar tissue

Autoimmune %epatitis

• About '0E of cases of chronic hepatitis

• )ot associated with viral infection

• Mostly in young women

• %igh titers of autoantibodies – antinuclear

– anti*smooth muscle

– anti*mitochondrial

• !n about of the cases they have an autoimmunedisease

disease

iver Abscess• &ocal collection of necrotic

tissue inflammatory

debris / fluid• $are in industriali3ed

nations

– usually due to bacteria or

fungi• Most caused by E!

histolytica

Toxic iver !nDury• 2ymptoms from imperceptible to fatal / onset from instantaneous to weeks afterexposure

• Mild inDury – asymptomatic – modest elevation of en3ymes

• 2evere inDury

– hepatic failure – hepatic coma – death

• 4ose related reactions – damage certain if enough chemicals present – uncommon – suicidal doses of acetaminophen

• Unpredictable toxic inDury – damage out of proportion to the dose – cannot metaboli3e a chemical as well as others – may initiate autoimmune hepatitis– drugs involved include

drugs involved include• sulfonamides• isonia3id• halothane

• May cause neoplastic growth

Alcoholic iver 4isease

• Alcoholism is the leading cause of liver diseasein industriali3ed nations

• About '0 million Americans abuse alcohol• About ';E of hospitali3ed patients have some

alcohol*related problem• Amount necessary to produce cirrhosis is about

'00gms?day for 10*1H years• 2eRuence of damage

– fatty liver

y – alcoholic hepatitis – cirrhosis

&atty iver

• 1st sign of alcohol

inDury

• aka steatosis

• -an be '*=] its si3eyellow greasy

• Usually asymptomatic

• May have elevated

en3ymes• %istologically see

-ouncilman bodies

Mallory bodies

Alcoholic %epatitis• 2ubacute or chronic form of alcohol liver inDury• -haracteri3ed by inflammation necrosis / early fibrosis• -an progress to cirrhosis• -linically

– malaise

– anorexia – $U pain – Daundice – elevated en3ymes – leukocytosis

• #ach bout has 10*'0E chance of death from – liver disease – intestinal hemorrhage – pancreatitis

• 2evere damage if abnormal clotting tests

– abnormal clotting tests – low albumin – signs of hepatic failure

• May not be reversible

Alcoholic -irrhosis• &inal / irreversible

stage of alcoholic

liver disease• :nly about 1;E of

alcoholics develop

• :ne of the leading

causes of liver

transplantation in

%emochromatosis• Toxic accumulation of iron in cells especially

liver heart / pancreas• rimary

– inherited autosomal recessive disorder – abnormally high absorption of &e from intestine – one of the most common inborn errors of metabolism

• 2econdary – acRuired – usually due to repeated transfusions given for sickle

usually due to repeated transfusions given for sicklecell thalassemia aplastic anemia

– chelate it to an excretable form

• Takes years to

accumulate enough

&e to cause damage

• -irrhosis if untreated

• 4iagnosis depends on

– clinical features

– increased blood levels of

&e ferritin transferrin – confirmed by liver biopsy

• rimary

– regular phlebotomy

• 2econdary – chelation of &e

Jilson 4isease

• Autosomal recessive disorder • Toxic accumulation of copper mainly in brain / liver • -opper absorbed in 9! tract / excreted in bile

– albumin transports to liver – bound to ceruloplasmin then secreted

– if biliary excretion decreases accumulates in liver /brain

• Manifests as behavioral oddities psychosis tremorsabnormal gait

• 4iagnosis confirmed by liver biopsy• #arly diagnosis critical• -helation therapy

%ereditary Alpha*1*Antitrypsin

4eficiency

• rotein made by liver

• Accumulate excessive amounts of defective AAT in

• :nly 10E of patients develop clinically significant

liver disease

• Autoimmune disease

• Usually have another

autoimmune disease• #volves from

inflammatory destructionof intrahepatic bile ducts

• #arly on seeaccumulation oflymphocytes around bileducts

• 4eath due to hepaticfailure / portal %T)

rimary 2clerosing -holangitis

• -hronic liver disease

• '?= of patients have ulcerative colitis

• !nflammation / fibrosis of intrahepatic / extrahepatic

bile ducts

• Typical patient is male under (0 with long*standing

ulcerative colitis

-irculatory 4isorders

• ortal vein obstruction as it flows into the liver – changes similar to portal %T) caused by cirrhosis

– usually due to thrombosis

• As it flows through the liver – most common cause is chronic passive congestion

usually with $ heart failure

• :bstruction in the hepatic vein as it flows out ofthe liver

hepatic vein thrombosis

– hepatic vein thrombosis

• !nfarcts uncommon

Metastatic -arcinoma

• Most common neoplasm in the liver

• Usually from colon lung breast

%epatocellular -arcinoma

• Usually related to %" / %-"

• %ematogenous metastases are common

• %igh levels of alpha fetoprotein• rognosis is grim

-holelithiasis

• 9allstones in the gallbladder or biliary tree

• &orm in gallbladder

• Usually have multiple stones

• About 1 million new cases?yr in U2

– ;0E reRuire surgery

• -holesterol gallstones

• >0E of cases

• ile saturated with

cholesterol

• -onditions associated

with their development

– age / gender

– weight

– ethnic hereditary /

geographic factors – drugs

– acRuired conditions

• igment gallstones

• '0E of cases

• &orm in gallbladder / in biliary tree

• -omposed of bilirubin / bile substances other thancholesterol

• Usually no symptoms until they begin to moveC mid*si3estones are the worst

• ainful cramps in $U

• )ausea?vomiting

• -omplications include – cholecystitis

– pancreatitis

– perforation

– empyema of gallbladder

Acute -holecystitis

• Most common maDorcomplication of

gallstones – G0E associated with

obstruction of the neck

• 9allbladder is

enlarged tense /inflamed

• ersistent rather mild$U i t

$U pain to verysevere pain

-hronic -holecystitis

• 4o not have to have a

history of acute attacks

• Almost always associated

with gallstones although

obstruction not necessary

• Mild to moderate $U

pain• )ausea?vomiting

• !ntolerance of fatty foods

:bstruction of the #xtrahepatic

ile 4ucts

'EPATIC 5ENIGNTUMORS

• 2imple hepatic cysts the most common are unilocularfluid*filled lesions that generally produce no symptoms.

• The possibility of echinococcosis should beconsidered.

• 2olitary cysts lined with cuboidal epithelium areclassified as cystadenomas and should be resectedsince they are premalignant.

Th f i di i f i i h i

• There are few indications for aspirating hepatic cysts.

• arge symptomatic cysts are difficult toeradicate with alcohol inDections and serioussuperinfection of the cyst cavity may occur.

• The simplest method consists oflaparoscopic cyst fenestration 7wide excision

of the cyst wall8.• A tongue of omentum is fixed so it lies in theresidual cyst cavity as an ancillary measureto prevent the edges from coapting

to prevent the edges from coapting.

Hepatic Adenoma

• oral contraceptives * 2mall adenomas may regress when agents arediscontinued

• Two*thirds are solitary

• Transition from benign to %-- may occur

• association of acute bleeding episodes with pregnancy.

• The general consensus is that adenomas should be resected becauseof the risks of malignant change and spontaneous hemorrhage.

• 2ymptomatic and large asymptomatic should be resected.

• #mergent resection or hepatic artery emboli3ation for hemorrhage.

-ocal *od%lar Hyperplasia

• young women

• oral contraceptive agents does not appear to predispose tothe development of &)%

• 2ymptomatic lesions should be removed while asymptomatictumors 7the maDority8 should be left undisturbed

• !nability to distinguish &)% from adenoma or malignantdisease is an indication for resection in some patients.

4i ti ti f l t ti b bl h i t

• 4iscontinuation of oral contraceptives probably has no impact.

HEPAT+, A6S,ESS

• bacterial parasitic or fungal in origin

• U2A pyogenic abscesses are the most common followed byamebic abscesses

• G0E of right lobe abscesses are solitary while only 10E of leftlobe abscesses are solitary.

• (0E of patients have an underlying malignancy

• ';E of cases no antecedent infection can be documented7[cryptogenic[ abscesses8.

• most cases the organism is of enteric origin

L+E1 -A+L1E

• Acute liver failure uncommon approx. ;000 new cases annually inthe U2.

• iver stellate cells 7!to cells8 are the principal mediators of fibrosis inthe liver and are stimulated by hepatocyte necrosis and cyto7ines 7tumor necrosis factor* interleukin*1 interleukin*H8 gro4thfactors 7epidermal growth factor platelet*derived growth factort f i th f t 18 l d b l t l t d O ff

Portal Hypertension

• )ormal pressure ranges from B to 10 mm %g.

• !n portal hypertension pressure exceeds 10 mm %g averagingaround '0 mm %g and occasionally rising as high as ;0,H0 mm%g.

• !n extrahepatic portal vein thrombosis 7without liver disease8collaterals in the diaphragm and in the hepatocolic

hepatoduodenal and gastrohepatic ligaments transport bloodinto the liver around the occluded vein 7hepatopetal8.

• !n cirrhosis collateral vessels circumvent the liver and deliverportal blood directly into the systemic circulation 7hepatofugal8C

portal blood directly into the systemic circulation 7hepatofugal8Cthese collaterals give rise to esophageal and gastric varices.

Portal Hypertension

• !solated thrombosis of the splenic vein causes locali3ed splenicvenous hypertension and gives rise to large collaterals from spleento gastric fundus.

• &rom there the blood returns to the main portal system through thecoronary vein.

• !n this condition gastric varices are often present withoutesophageal varices.

• spontaneous bleeding is relatively uncommon except from those atthe gastroesophageal DunctionC spontaneous bleeding from gastric

varices can sometimes occur.• -ompared with adDacent areas of the esophagus and stomach thegastroesophageal Dunction is especially rich in submucosal veinswhich expand disproportionately in patients with portal hypertension.

• The cause of variceal bleeding is most probably rupture due to

g ysudden increases in hydrostatic pressure.

Pri/$r+ Liver C$ner

• iver malignancy may arise from

– %epatocytes

– iliary epithelial cells

1is7 -actors ( H,,

• -hronic %" and %-"

• -irrhosis

• -hronic underlying liver disease.

1is7 -actors ( cholangio,A

• !nfreRuently associated with cirrhosis.

• rimary sclerosing cholangitis

• Jidespread infection with liver flukes 'Clonorchissinensis

• A large proportion of patients will have intra* or extra*hepaticmetastases at presentation.

• infiltration of the portal venous system with subseRuentdissemination of tumor cells.

• "ascular invasion is more common with larger tumors 7S ; cm8.

• Most common mets include the hilar and celiac lymph nodesd th l t t t b d b i l

and the lungsC metastases to bone and brain are less commonand peritoneal disease 7ie carcinomatosis8

• percutaneous core biopsy or aspiration biopsy.

• &ine*needle aspiration

• A negative result therefore does not rule out malignantdisease

• !n patients with cirrhosis the presence of a hypervascularmass S ' cm on two different imaging studies or ahypervascular mass S ' cm on one imaging study combinedwith a serum alpha fetoprotein level S (00 ng?m is dx of

with a serum alpha*fetoprotein level S (00 ng?m is dx of%--

T%mor Mar7er ( A-P

• hepatomas and testic%lar t%mors.

• %pper limit of normal is 5" ng=mLO

• val%es above 5"" ng=mL are s%ggestive of

hepatoma

• R>"" ng=mL in a cirrhotic patients 4ith ahypervasc%lar liver mass R 5 cm in diameter are dx.

hypervasc%lar liver mass R 5 cm in diameter are dx.

METASTAT+, *E/PLASMS

• 5" times more common than primary t%mors in theliver

• via the systemic or portal veno%s circ%lation

• colon& pancreas& esophag%s& stomach&ne%roendocrine& breast& l%ng& 7idney& adrenal& ovaryand %ter%s& melanoma& and sarcomas

• Tx most R chemotherapy is the only treatment option

• most effective therapy

• minimal criteria disease confined to the liver disease amenable to a complete resection.

• &or small and peripherally placed lesions sublobarsegmental resections are preferred

• Anatomical segmentectomies are preferred to non*

Anatomical segmentectomies are preferred to nonanatomical resections.

• cirrhosis constitutes the maDor obstacle to resection in

patients with %--.

• -areful patient selection

•cirrhotic patients have a late risk of death

• highly selected patients may be better treated with livertransplantation rather than resection.

Metastasis

Diret inv$,ion

L+/* node di,,e/in$tion

5-ood ,re$d

Intr$eritone$- o-oni:$tion

L+E1 -A+L1E

• Acute liver failure uncommon approx. ;000 new cases annually inthe U2.

• iver stellate cells 7!to cells8 are the principal mediators of fibrosis inthe liver and are stimulated by hepatocyte necrosis and cyto7ines 7tumor necrosis factor* interleukin*1 interleukin*H8 gro4thfactors 7epidermal growth factor platelet*derived growth factortransforming growth factor 18 released by platelets and Oupffer

iver &ailure

Mackay Memorial %ospital

4epartment of !nternal Medicine4ivision of 9astroenterology

$( 陳泓達

BJ9J!!

• iver failure+

-linical syndrome+ sudden loss ofliver

parenchymal and metabolic function

Manifest as coagulopathy and

encephalopathy

• Acute liver failure +

4efined as interval between onset of the illness and

appearance of encephalopathy N > weeks

• #tiology+

Jestern countries+ heterogenous drugs

7acetaminophen )2A!48 viruses

4eveloping countries+ viruses regional

4ifference 7endemic area <8

5ournal o% 6astroenterology and Hepatology 7'00'8#I&

2'H>,2'B=

Acetaminophen toxicity

!diosyncratic drug toxicity

%epatotropic viruses

Miscellaneous causes

!ndeterminate acute liver failure 7viruses can not be

demonstrated < 8

• Uncommon causes+

Jilson6s disease other infections 7-M" %2"

#"8 vascular abnormality toxin acute fatty liver

of pregnancy antoimmune hepatitis ischemia

malignant infiltration

• 2ymptoms and signs+

Iaundice altered mental status nausea?

vomiting anorexia fatigue malaise

myalgia?arthralgia

Most of them present hepatoencephalopathy

and icteric appearance.

%ypoglycemia

#ncephalopathy

!nfections

%emorrhage

-oagulopathy

%ypotension7hypovolemia vascular resistance X8$espiratory failure

$enal failure

ancreatitis

• %ypoglycemia+ monitoring blood glucose !" glucose

supplement.

• !nfection+ aseptic care high index of suspicionpreemptive antibiotic.

• %emorrhage 7i.e. 9!8+ )9 placement %' blocker or

• %ypotension+ hemodynamic monitoring or centralpressures volume repletion

• $espiratory failure 7A$428+ mechanical ventilation.

• $enal failure 7hypovolemia hepatorenal syndrome

AT)8+ hemodynamic monitor central pressurevolume repletion avoid nephrotoxic agent

#ncephalopathy

• maDor complication

• precise mechanism remains unclear

• %ypothesis+ Ammonia production

• Treatment toward reducing ammonia production

• Jatch out airway prevent aspiration

#ncephalopathy

• 2tage 1+ day*night reversal mild confusion

somnolence

• 2tage '+ confusion drowsiness

• 2tage =+ stupor

• 2tage (+ coma

#ncephalopathy

redisposing factor of hepatic encephalopathy+

9! bleeding increased protein intake hypokalemic

alkalosis hyponatremia infection constipation

hypoxia infection sedatives and tranRuili3ers

#ncephalopathy

T %pon ammonia hypothesis

• -orrection of hypokalemia

• $eduction in ammoniagenic substrates+ cleansing

enemas and dietary protein restriction.

• actulose+ improved encephalopathy but not

improved outcome.

4ose '*= soft stools per day

#ncephalopathy

• :ral antibiotics+ neomycin lack of evidence

nephrotoxicity limited use.

-erebral #dema

• -erebral edema develops in B; * >0 E of patients

with grade !" encephalopathy.

• precise mechanism + not completely understood

• ossible contributing factor+

osmotic derangement in astrocytes

changes in cellular metabolism

alterations in cerebral blood flow

-erebral #dema

Yintracranial pressure 7!-8 and brainstem

%erniation the most common causes of death

in fulminant hepatic failure

ischemic and hypoxic inDury to the brain

hypertension bradycardia and irregular respirations Y muscle tone hyperreflexia

-erebral #dema

• Monitoring of !-+

routinely used by more than one*half of liver

transplantation programs in the United 2tates

• Tx+ to maintain !- below '0 mm%g and the -

above ;0 mm%g.

-oagulopathy

• diminished capacity of the failing liver to synthesi3e

coagulation factors.

• The most common bleeding site+ 9! tract.

• rophylactic administration of &&+ not

recommended.

performed before transplant or invasive procedure

2pecific Treatment

• A-T intoxication+ charcol followed by )A-

• 4rug induced hepatotoxicity+ discontinue drugs

supportive treatment

• "iral hepatitis+

%"+ anti*%" treatment lamivudine

%2"?varicella 3oster+ acyclovir others+ supportive care

• Jilson6s disease+ early diagnosis liver transplant

• autoimmune hepatitis+ confirm diagnosis 7liver

biopsy8 corticosteroid liver transplant

• acute fatty liver of pregnancy or the %#

syndrome+ obstetrical services and expeditious

delivery are recommended

• Acute ischemic inDury 7shock liver8+ cardiovascular

support

• Malignant infiltration+ liver biopsy for diagnosis

treat underlying disease.

• !ndeterminate etiology+ consider biopsy for diagnosis

and further guide of treatment

iver transplant

• iver transplant+ remain backbone of treatment of

fulminant hepatic failure

reliable criteria to identify these patients who reallyneed transplant.

remain unresolved in fulminant hepatic failure.

At Oing6s -ollege hospital in ondon 7not due to A-T8

either TS100 second

or the presence of any three of the following variables+

1. age N 10 or S (0 years C

'. an etiology of non*A non* hepatitis halothane

drug induced liver failureC=. duration of Daundice before onset of encephalopathy

S B days prothrombin time S;0 s and serum

bilirubin S =00 mmol?.

#ncephalopathy

-oagulopathy 7T8

iver transplant

• -riteria+

!n chronic liver disease

most commonly used prognostic modelM#4 score 7Model for End(stage Liver

Disease 8

=.>_n serum bilirubin 7mg?d8` V 11.'_n !)$`

V G.H_n serum creatinine 7mg?d8` V H.( n+ natural logarithm.

iver transplant

• ,/*T1A+*D+,AT+/*S+

1. -ardiopulmonary disease can not be corrected or

preclude surgery.

'. Malignancy outside of the liver within ; years of

evaluation or can not be cured.

=. Active alcohol and drug use

• Advanced age and %!" disease+ relative contra*

indication 7site*specific management8

iver support system

• )on*cell*based+ plasmapheresis and charcoal*based

hemoabsorption

• -ell*based systems + known as bioartificial liversupport systems

iver support system

• )on*cell*based+ not improved survival.

Available systems+

molecular adsorbents recirculation system 7MA$28

• -ell*based systems+ undergoing trial.

Acute iver &ailure

&oie 9ras

• -oie gras 7pronounced ?fw r ?ɑːˈɡ ɑː in #nglishC &rench

for [fat liver[8 is a food product made of the liver of a

duck or goose that has been specially fattened.

&unctions of the iver

• Metabolic

– -arb metabolism

– rotein and lipoprotein metabolism – &atty acid metabolism

– iotransformation of drugs

• 2torage

– 9lycogen – "itamins A 4 # and O

– !ron and copper

Functions o the Liver

• mmunolo!ical unction s – "#nthesis o immuno!lobulins

– $ha!oc#tosis b# %upfer cells – Filtration o bacteria

– &e!radation o endoto'ins

• ('cretion o bilirubin and urea ormation

• )aematolo!ical unctions – *lood reservoir

– )aematopoiesis in the oetus

F 2yndrome that leads to M:& and

deathoreviously normal liver may fail withindays

F %igh grade encephalopathy

survival is N'0EF #arly death+o cerebral oedema -"2 collapse

F ate death+o

4efinition and -lassifications

F A&+ 2d. defined byo #ncephalopathyo -oagulopathyo Iaundiceo !ndividual with previously normal liver

F &ulminant %epatic &ailureo otentially reversible conditiono -onseRuence of severe liver inDuryo #ncephalopathy appears within > wks. of

initial 2x.o Absence of pre*existing liver ds.

F Oing6s classification+o %yperacute+ encephalopathy within NB days

aracetamol ischaemic viral toxinso Acute+ >*'> dayso 2ubacute+ ;*'H weeks 2eronegative idiopathic drug*related

4ifferent etiology oorer prognosis

#tiology

,a%se Agent 1esponsible

iral Hepatitis Hep. A& 6& D& E& ,M& HS& seronegative

hepatitis 2#>(5!C in 3

Dr%g(related Dose(related& e.g.paracetamolO idiosyncraticreactions& e.g. anti(T6& statins& recreationaldr%gs& anticonv%lsants& *SA+Ds& many others

Toxins ,arbon tetrachloride& a!anita phalloides

asc%lar events +scahemic hepatitis& veno(occl%sive disease&6%dd(,hiari& heatstro7e

/ther Pregnancy(related liver disease& ilson?sdisease& lymphoma& carcinoma& tra%ma

#tiology

F Most common causes+o Jorldwide+

%epatotrophic viruses A*#o UO aracetamol overdose 2eronegative or non*A*# hepatitis

!diosynchratic drug rxs. or Jilson6s ds.

Jorkup

F !dentify the etiologyo %x. examination viral and autoimmune

profilesF loods

o &- #U- -M coags &Ts drug levels

F Abdo U29 and -To "ascular pattern ascitis splenomegaly

Jorkup

F iver x.o 4one by transDugular routeo Mays suggest specific 4x.o Jatch for sample from healthy liver o S;0E necrosis assoc. with poor prognosiso )eed to reverse coagulopathy before doing

athophysiology

F %epatic encephalopathyo alteration in mental status and cognitive function occurring in

the presence of liver failure

F iver failure leads to+o portal %T)o splachnic vasodilationo %ypoalbuminaemiao $educed plasma oncotic pressureo

eads to ascitis and organ oedema

athophysiology

F 4ecreased intravascular volumeo Oidneys try to @compensate and retain )aV

and water making oedema worseF AlsoF 9ut*derived toxins reach the liver

o Ammonia levels are often higho -orrelation between ammonia and

symptoms is poor

-linical &eatures

F 4epend on the severity which dependson+o #tiologyo 2peed of onset of symptoms

F )on*specifico )/" abdo pain

F )eurologicalo -onfusion agitation coma

2cale :f %epatic #ncephalopathy

;rade Level of ,onscio%sness Personality and +ntellect *e%rologic Signs Electroencephalogram2EE;3 Abnormalities

" *ormal *ormal *one *one

S%bclinical

*ormal *ormal Abnormalities only on psychometrictesting

# Day=night sleep reversal&restlessness

-orgetf%lness& mild conf%sion& agitation&irritability

Tremor& apraxia& incoordination& impairedhand4riting

Triphasic 4aves 2! H'3

5 Lethargy& slo4edresponses

Disorientation to time& loss of inhibition&inappropriate behavior

Asterixis& dysarthria& ataxia& hypoactivereflexes

< Somnolence& conf%sion Disorientation to place& aggressivebehavior

Asterixis& m%sc%lar rigidity& 6abins7isigns& hyperactive reflexes

> ,oma *one Decerebration Delta=slo4 4ave activity

-linical &eatures

F Mortality is higher for 9rade !!!?!"o Mostly due to cerebral oedemao :ccurs in >0E of pts. w?A&4ue to lack of eRuilibration of osmotic gradient =0E of those have cerebellar tonsil and?or

temporal lobe herniation causing deatho

Je6re now better at treating cerebraloedema

-linical &eatures

F #levated !-o %T) bradycardia blown pupils+ occur lateo -T won6t tell youo !- monitor is best way of knowing

F -"2 changeso 2imilar to sepsiso Might be due to infection

-linical &eatures

F $enal failureo :ligurico oor prognosis #xcept with paracetamol overdose where it has

a good prognosis

F !mpaired immunityo 4ecreased complement synthesis Oupffer

cell dysfunction poor neutrophil adhesionand superoxide production

-linical &eatures

F !ncreased susceptibility to infectiono >0E of pts. have bacteriologically proven

infectionso MaDor sepsis is contributor to death in '0E

of cases 2taph. aureus B0E of gram 7V8

#. -oli most common gram 7*8-. albicans in =0E of pts.

Monitoring

F ts. need %4U?!-UF )eed -"- and continuous !

monitoring and !4-F aseline A9 and lactate

o actate S=mmo? after adeRuate resus hassame sensi. and speci. for death as TheOing6s -ollege %ospital criteria

rognosis

F Early indicators of prognosis in f%lminant hepatic fail%re. :59rady I9 Alexander 9I %ayllar OM Jilliams $. 6astroenterology . 1G>G AugCGB7'8+(=G*(;.

F Oing6s -ollage %ospital -riteriao :riginally devised as prognostic criteria to predict patient survival

without liver transplanto )ow used as selection criteria for potential liver transplant recipients

O-% -riteria

F Patients 4ith paracetamoltoxicityo p% NB.= 7B.'; if given )A-8

:rall three of the following+o rothrombin time S100so 2erum creatinine level S=00

mol?lo 9rade !!! or

!"encephalopathy

F /ther patientsF Prothrombin time R#""

seconds or Three o# the #ollowingvariableso Age #" yr or R>" yr o 9a%ndice RI days before

encephalopathyo PT R !"so 6ilir%bin R <""mmol=L

O-% -riteria

• ositive predictive value for !-U death without

transplantation of 0.G>

• )egative predictive value of 0.>'

Treatment

F +ntensive care of patients 4ith ac%teliver fail%re recommendations of the

.S. Ac%te Liver -ail%re St%dy;ro%p.

2travit3 $T Oramer A% 4avern T 2haikh A:-aldwell 2% et al.

Critical Care Medicine '00BC <! '(G>*;0>

Treatment

F Adult U.2. Acute iver &ailure 2tudy9roupo 4ata from '= liver transplant centers S1110 pts.

o !n '00; convened to

review literature on management-are of pts. w?high !-s-ompare practices of different centers

9eneral Management

F Admit to hospital and %4U?!-Uo Jhen evidence of A&

#.g.+ !)$S1.;o 4?J+ hysician !ntensivist)earest transplant center $egarding best time to refer

9eneral Management

F #tiology*specific treatmento 2tudies only for paracetamol overdoseo )A- regardless of time of overdose !" if 9rade ! encephalopathy%ypotension Any other reason : )A- is not tolerated

%# or acute fatty liver of pregnancy Tx. !s immediate delivery

9eneral Management

F )A-o 1;0mg?kg !" in '00ml )2 over 1;*H0minso ;0mg?kg !" over (hrso 100mg?kg !" over 1Hhrs Total dose+ =00mg?kg over '0hrs

o !nfusion recommended until there is

evidence of improved hepatic functionrather than time or paracetamol levels

Management of -omplications

F %epatic encephalopathy and hyperammonaemiaF !nfectionsF 2edation and analgesia

F leeding diathesisF )utritionF 2ei3uresF -irculatory dysfunction

#ncephalopathy

F 2tandard treatment+o actulose

Jatch for+ Abdo distension :esophageal varices will need a scope

Avoid intravascular depletion

o )on*absorbable ATs)eomycin not recommended by A&29

because of nephrotoxicity

!nfection prophylaxis and surveillance

F !nfection is one of main causes of death in A&F Most common sites+

o ungo Urinary tracto lood

F Most common M.:.o 9ram 7V8 cocci+ 2taph aureuso 9ram 7*8 rods+ #. colio &ungi+ candida

!nfection prophylaxis and surveillance

F #mpirical ATs are recommended by A&29 when+o 2urveillance cultures reveal significant isolateso Advanced stage 7!!!?!"8 encephalopathyo $efractory hypotensiono 2!$2

F =rd gen. -ephalosporin or Timentin "ancomycin &lucona3ole

2edation and analgesia

F Agitation contributes to raised !-F ropofol vs. en3os

o oth increase 9AA neurotransmission therefore may exacerbateencephalopathy

o ropofol decreases !- and wears off Ruickly

F :pioidso 2horter acting are preferableo Jhen there is concommitant A$& avoid morphine or pethidine due

to metabolite accumulation

-orrection of bleeding diathesis

F ts. with A& are by definition coagulopathico ow plts. and fibrinogen "it. O deficiento 2pontaneous bleeding is rare

F "ery difficult to obtain complete correctionF A&29 recommends aiming for+

o !)$ 1.;o lts. ;0000

F rophylactic && not recommendedo :bscures the trend of T as prognostic marker

F -ryo recommended when fibrinogen low

F Jhen && fails to correct T?!)$ then recombinant factor "!!acan be giveno 2hould be given before planned procedureso Avoid in patients with risk of thrombotic complication

M! 4"Ts etc.

F ;+ bleedingo red%ced by H5 antagonists or PP+s

F TEDS and Sc%ds

)utrition

F A& is a catabolic stateo )egative nitrogen balance

o !mmunodeficiencyF #nteral nutrition when possible

o %i*calo Avoid free water and hypo*osmolarity

F T) when+o 2pecific contraindication for enteral feeds

2ei3ure rophylaxis and 2urveillance

F )onconvulsive sei3ure activity is commono rophylactic antiepileptics not recommendedo ##9 when+

9rade !!?!" encephalopathy

2udden neuro deterioration Myoclonus To titrate use of barbiturates

F Tx.o henytoino ropofol mida3 barbiturates

-"2 4ysfunction

F -orrect hypovolaemia before starting vasopressorsF ressors needed for hypotension and low -

o )orad is first line can give high dose dopamineo Adrenaline may compromise %&o "asopressin not recommended because directly causes cerebral

vasodilation and high !-s

F Medium doses of steroid may improve pressor response

Mx. of -erebral :edema and!ntracranial %ypertension

F $aised !- due to cerebral oedema isone of maDor causes of M/M

F -T for 9rade !!!?!"o To rule out anything else i.e. bleed

F !- monitor o 9rade !!!?!" encephalopathyo To optimi3e -o )ot routine

$aised !-

F Aim for o !-N';mm%g

o - ;0*>0F 9eneral recommendations

o Oeep it Ruiet minimi3e chest physio and#TT suctioning head at =0o

o 4on6t treat spontaneous hyperventilationkeep a-:' =;*(0mm%g treat feveraggressively with physical measures

$aised !-

F 2pecific managemento Manitol+ first line therapy

o %ypertonic 2alineo !nduced hypothermiao arbiturate comao !ndomethacin+ ';mg !" over 1min.

Mechanical "entilation

F Jhen to intubate+o $espiratory failure

o Airway protection in advancedencephalopathy

o Agitationo !mminent !- monitor placement

Mechanical "entilation

F ts. w?A& often develop A!?A$42o &ollow A$42)et protocol

o Avoid high ##Use the minimum needed

F !ndicated for+o $enal failure

o &luid overloado Metabolic derangementso )eed to create space for !" colloids i.e.

F -$$T preferred over !$$To %4 instability common

F Use citrate over heparino Monitor ioni3ed calcium

F Use bicarb buffer over lactate or citratebuffer o iver won6t be able to convert them to

F Avoid hyponatraemiao May exacerbate cerebral oedema

iver Transplant

• :rthotopic liver transplant is the definitive treatment

for patients who meet the criteria

– orZthoZtopZic 7rth*tpk8ad4!!n the normal or usual position• 1 yr. and ; yr . survival of patients undergoing :T for

A& is about '0E lower than elective cases for

cirrhotic patients

• Auxiliary liver transplantation is and alternative

iver Transplant

• Absolute contraindications

– :verwhelming sepsis

– $efractory hypotension – A!42

– Uncontrolled raised !- with likely permanent damange

%epatic assist devices

• MA$2+ molecular absorption and recirculation

system

– Adaptation of haemodialysis – lood is dialysed against '0E albumin

• 2hown to improve encephalopathy renal function and

haemodynamic parameters

– The efficacy of this techniRue has not yet been studied

2o what have we learned<

Thank you

)($+,.(LL/L+0 .+0.12+

(pidemiolo!#

• )epatocellular carcinoma is the 3th most common

mali!nanc# 4orld4ide 5 the =rd cause of cancer related

death 4ith male-to-emale ratio

, 3:6 in +sia

, 7:6 in the /nited "tates

• ,umor incidence varies si!ni8cantl#9 dependin! on!eo!raphical location.

• %-- with age.

– ;= years in Asia

– HB years in the United 2tates.

!ncidence of %--

#tiology

• )epatitis *)epatitis *

-!*"reae r!% 100 -200 &old

- 90 o& HCC are po!t!e &orHB g

• )epatitis .)epatitis .

• .irrhosis.irrhosis

- ;< o ).. arise on top- ;< o ).. arise on top

o cirrhosiso cirrhosis

!ncidence according to etiology

A&&revi$tion,> D% i-,onK, di,e$,e? P5C% ri/$r+ &i-i$r+ irr*o,i,% ''% *eredit$r+ *e/o*ro/$to,i,?'5V * titi 5 i i f ti 'CV * titi C i i f ti

'5V% *e$titi, 5 viru, infetion? 'CV% *e$titi, C viru, infetion.

2igns / symptoms

• )onspecific symptoms)onspecific symptoms – abdominal pain

– &ever chills

– anorexia weight loss

– Daundice

• hysical findingshysical findings – abdominal mass in one third

– splenomegaly

– ascites

– abdominal tenderness

9uidlines

7a8 which patients are at high risk for the development of %--

and should be offered surveillance

7b8 what investigations are reRuired to make a definite

diagnosis

7c8 which treatment modality is most appropriate in a given

clinical context.

9uidlines

- 8 $!th eta'l!hed "!rrho! de to HB a*d) or HC, part!"larly thoe $!th

o*go!*g !ral repl!"at!o*

- 8 $!th eta'l!hed "!rrho! de to ge*et!" hae(o"hro(ato!

- 8 $!th al"ohol related "!rrho! $ho are a't!*e*t &ro( al"ohol or l!%ely to"o(ply $!th treat(e*t

- 8 $!th pr!(ary '!l!ary "!rrho!

A&do/in$- US $nd AFPJ 9

/ont*,

(a' 5hi#h +atients are at high ris for

the &e!elo+ment of * 7 shol& 4e

offere& sr!eillan#e

/ont*,

4iagnosis

'b7 0hat in.estigations are re8uired to ma*e a de%inite diagnosis

18 A& produced by B0E of %--

S (00ng?ml A& over time

'8 !maging

* focal lesion in the liver of a patient with cirrhosis is highlylikely to be %--

* 2piral -T of the liver

* M$! with contrast enhancement

M$! with contrast enhancement

4iagnosis

=8 iopsy is rarely reRuired for diagnosis

in 1,=E.

iopsy of potentially operable lesionsshould be avoided where possible

,eedin

4iagnosis

Cirr*o,i, @

M$,, ! /

Confir/r

4iagnosis

Cirr*o,i, @ M$,,

Nor/$-

A,,e,, for

,urer+

CT% MRI

-e,ion &+ e3$/

FNAC or &io,+Confir/ed

di$no,i,

Treatment 72urgery8

• The only proven potentially curative therapy for %--

• %epatic resection or liver transplantation

• atients with single small %-- 7; cm8 or up to three lesions = cm

• !nvolvement of large vessels 7portal vein !nferior vena cava8 doesntautomatically mitigate against a resectionC especially in fibrolamellar

histology

• )o randomised controlled trials comparing the outcome of surgicalresection and liver transplantation for %--.

Treatment 72urgery8

• %epatic resection should be considered in %-- and a non*cirrhotic

liver 7including fibrolamellar variant8

• $esection can be carried out in highly selected patients with

cirrhosis and well preserved hepatic function 7-hild*ugh A8 who areunsuitable for liver transplantation. !t carries a high risk of

postoperative decompensation.

• erioperative mortality in experienced centres remains between HE

and '0E depending on the extent of the resection and the severity ofpreoperative liver impairment.

• The maDority of early mortality is due to liver failure.

Treatment 72urgery8

• $ecurrence rates of ;0,H0E after ; years after resection are usual

7intrahepatic8

• iver transplantation should be considered in any patient with

cirrhosis

• atients with replicating %"? %-" had a worse outlook due to

recurrence and were previously not considered candidates for

transplantation.

• #ffective antiviral therapy is now available and patients with small

%-- should be assessed for transplantation

should only be used where surgical therapy is not possible.

18 ercutaneous ethanol inDection 7#!8

• has been shown to produce necrosis of small %--.• !t is best suited to peripheral lesions less than = cm in

diameter

'8 $adiofreRuency ablation 7$&A8

• %igh freRuency ultrasound to generate heat• good alternative ablative therapy

• )o survival advantage

• Useful for tumor control in patients awaiting liver transplant

=8 -ryotherapy

• intraoperatively to ablate small solitary tumors outside a

planned resection in patients with bilobar disease

(8 -hemoembolisation

• -oncurrent administration of hepatic arterial chemotherapy

7doxirubicin8 with emboli3ation of hepatic artery

• roduce tumour necrosis in ;0E of patients

• #ffective therapy for pain or bleeding from %--

• Affect survival in highly selected patients with good liver

reserve

• -omplications+ 7pain fever and hepatic decompensation8

;8 2ystemic chemotherapy

– very limited role in the treatment of %-- with pooresponse rate

– est single agent is doxorubicin 7$$+ 10* '0E8

– -ombination chemotherapy didn6t response butsurvival

– should only be offered in the context of clinical trials

H8 %ormonal therapy

- )olvadex stilbestrol and flutamide

B8 !nterferon*alfa

>8 retinoids and adaptive immunotherapy 7adDuvant8

Targeted therapy for %--

2election of agents for targeted

therapy in %--*ame Target

;efitinib

Erlotinib

Lapatanib

,et%ximab

6evaci'%mab

Sorafenib 2*exavar3

S%nitinib

atalanib,ediranib

1apamycin

Everolim%s

6orte'omib 2elcade3

1af#& 6(1af& E;-1 & PD;-1

PD;-1& E;-1& c(+T& -LT(<

E;-1& PD;-1& c(+TE;-1

mT/1 2mammalian target of rapamycin8

Proteasome

Targeting angiogenesis for %--

• %-- is one of the most vascular tumor %-- is one of the most vascular tumor

• MaDor driver of angiogenesis is vascular endothelial growthMaDor driver of angiogenesis is vascular endothelial growth

factor 7"#9&8factor 7"#9&8

• 2orafenib and bevace3umab target "#9& in %--2orafenib and bevace3umab target "#9& in %--

• evaci3um3b+ Median :2 of approximately 1' monthsevaci3um3b+ Median :2 of approximately 1' months

• evaci3umab V erlotinib+ Medain :2 1;*1B monthsevaci3umab V erlotinib+ Medain :2 1;*1B months

!nvestigational combination therapies

in %--

• -ombinations under investigations-ombinations under investigations

– evaci3um3b V erlotinib

– 2orafenib Verlotinib

• -ombination therapy will likely be used to treat %---ombination therapy will likely be used to treat %--

in the futurein the future

%-- 7Jhats ahead<8

• -ombinations therapy

• evaci3um3b or 2orafenib V #rlotinib

• 2orafenib V mT:$ inhibitor

• #arly seRuential therapies

GASTROENTEROLOGY GASTROENTEROLOGY

Universitatea Titu MaiorescuUniversitatea Titu Maiorescu

BucurestiBucuresti

Liver Disorder Liver Disorder s ands and Biliary Tract DiseaseBiliary Tract Disease

Lecture IIILecture III

Prof Univ Dr Ion C. intoiuProf Univ Dr Ion C. intoiu

Ga!!"!adderGa!!"!adderDisordersDisorders

ANATOMY # ANATOMY #

P$YSIOLOGY P$YSIOLOGY BILIARY SYSTEMBILIARY SYSTEMa.a. Canaliculi – the smallest bile ducts locatedCanaliculi – the smallest bile ducts located

between liver lobules receive bile !rombetween liver lobules receive bile !romhe"atoc#tes. The canaliculi !orm lar$er bilehe"atoc#tes. The canaliculi !orm lar$er bile

ducts which lead to he"atic duct.ducts which lead to he"atic duct.b.b. %e"atic duct – !rom the liver &oins the c#stic%e"atic duct – !rom the liver &oins the c#sticduct !rom the $allbladder to !orm the commonduct !rom the $allbladder to !orm the commonbile duct which em"ties into the duodenum.bile duct which em"ties into the duodenum.

c.c. S"hincter o! 'ddi – controls the (ow o! bileS"hincter o! 'ddi – controls the (ow o! bileinto the intestine.into the intestine.

d.d. )allbladder – is a hollow "ear*sha"ed or$an)allbladder – is a hollow "ear*sha"ed or$anthat is +,*-,mm lon$. ormall# holds +,*/,mLthat is +,*-,mm lon$. ormall# holds +,*/,mLo! bile and can hold u" to 0,mL when !ull#o! bile and can hold u" to 0,mL when !ull#distended.distended.

%ILIARY SYSTEM%ILIARY SYSTEM

1rainin$ bile !rom he"atoc#tes to1rainin$ bile !rom he"atoc#tes to

the $allbladder b# wa# o! biliar# treethe $allbladder b# wa# o! biliar# tree

Storin$ bile in the $allbladder andStorin$ bile in the $allbladder andreleasin$ it to the duodenum whichreleasin$ it to the duodenum which

is mediated b# the hormoneis mediated b# the hormone

cholec#sto2inin*"ancreo3#min.cholec#sto2inin*"ancreo3#min.

T&e Ga!!"!adder T&e Ga!!"!adder

Located below the liverLocated below the liver

The c#stic duct &oins the he"aticThe c#stic duct &oins the he"atic

duct to become the bile ductduct to become the bile duct The common bile duct &oins theThe common bile duct &oins the

"ancreatic duct in the s"hincter o!"ancreatic duct in the s"hincter o!

'ddi in the 4rst "art o! the'ddi in the 4rst "art o! theduodenumduodenum

Stores and concentrates bileStores and concentrates bile

Contracts durin$ the di$estion o!Contracts durin$ the di$estion o!

!ats to deliver the bile!ats to deliver the bile CholecystokininCholecystokinin is released b# theis released b# the

duodenal cells causin$ theduodenal cells causin$ the

contraction o! the $allbladder andcontraction o! the $allbladder andrela5ation o! the s"hincter o! 'ddirela5ation o! the s"hincter o! 'ddi

C$OLELIT$IASISC$OLELIT$IASIS

Re!ers to !ormation o! calculi 6ieRe!ers to !ormation o! calculi 6ie$allstones in the bladder.$allstones in the bladder.

7redis"osin$ 8actors97redis"osin$ 8actors9:.:. 'bese'bese

;.;. 8emale8emale

<-, #rs<-, #rs-.-. 'C Estro$en inta2e'C Estro$en inta2e

/./. 8air8air

C$OLELIT$IASISC$OLELIT$IASIS

"upersaturated bile9 *iliar# stasis

"tone ormation

*loc=a!e o >allbladder

nammation9 2ucosal &ama!e and W*.in8ltration

.)L(.@",,"

Co''on !ocations of (a!!stonesCo''on !ocations of (a!!stones

C$OLECYSTITISC$OLECYSTITIS

–– in(ammation o! $allbladder within(ammation o! $allbladder with

$allstone !ormation.$allstone !ormation.

C%'LECYSTITIS=C%'LECYSTITIS=

C%'LELIT%IASISC%'LELIT%IASIS

Si$ns and S#m"toms9Si$ns and S#m"toms9 Severe Ri$ht abdominal "ain radiatin$ toSevere Ri$ht abdominal "ain radiatin$ to

the bac2 the bac2

8ever8ever 8at intolerance8at intolerance Anore5ia n=v Anore5ia n=v >aundice >aundice

7ruritus7ruritus Eas# bruisin$Eas# bruisin$ Tea colored urineTea colored urine SteatorrheaSteatorrhea

C%'LECYSTITIS=C%'LECYSTITIS=

C%'LELIT%IASISC%'LELIT%IASIS

1ia$nosis91ia$nosis9

?S detects the "resence o! $allstone?S detects the "resence o! $allstone

Serum al2aline "hos"hatase – /,*Serum al2aline "hos"hatase – /,*:;, u=L:;, u=L

@BC@BC

Endosco"ic retro$radeEndosco"ic retro$radecholan$io"ancreato$ra"h# 6ERC7 *cholan$io"ancreato$ra"h# 6ERC7 *

C$OLELIT$IASIS)C$OLECYSTITIC$OLELIT$IASIS)C$OLECYSTITI

Sur$ical "rocedures* Sur$icalSur$ical "rocedures* Sur$ical

Cholec#stectom# Choledochotom#Cholec#stectom# Choledochotom#

La"arosco"ic cholec#stectom#La"arosco"ic cholec#stectom#

C$OLELIT$IASIS)C$OLECYSTIC$OLELIT$IASIS)C$OLECYSTI

TISTIS

7ost*o"erative nursin$ interventions7ost*o"erative nursin$ interventions

:. Monitor !or sur$ical com"lications:. Monitor !or sur$ical com"lications

;. 7ost*o"erative "osition a!ter recover# !rom;. 7ost*o"erative "osition a!ter recover# !romanesthesia*anesthesia* LOW FOWL!"s LOW FOWL!"s

+. Encoura$e earl# ambulation+. Encoura$e earl# ambulation-.-. Administer medication #efore co$ghing and Administer medication #efore co$ghing and

dee% #reathing e&ercisesdee% #reathing e&ercises/. Advise client to s"lint the abdomen to/. Advise client to s"lint the abdomen to

"revent discom!ort durin$ cou$hin$"revent discom!ort durin$ cou$hin$

. Administer anal$esics antiemetics. Administer anal$esics antiemeticsantacidsantacids

0. Care o! the biliar# draina$eor T*tube0. Care o! the biliar# draina$eor T*tubedraina$edraina$e

. 8at restriction is onl# limited to -* wee2s.. 8at restriction is onl# limited to -* wee2s.ormal diet is resumedormal diet is resumed

T*$n6 +ou

9A2T$:#)T#$::9Z

niversitatea Tit% Maioresc%

ucuresti

LE,T1E

Prof niv Dr +on ,. intoi%Ț

PAT'OLOG OF T'EPAT'OLOG OF T'E

PANCREASPANCREAS##

++. Detailed Anatomy

A. andmark structures

1. 2plenic Artery+

a. ranch of celiactrunk

b. passes right to

c. -ourse is alongupper margin of

body and tail

Arterial S%pply to Pancreas

Co!!on

Hepatic (rtery

roper Hepatic (rtery

$uperior*esenteric

(rtery

Detailed Anatomy contin%ed

. Head of Pancreas

+ Head , ody and Tail o# ancreas

1+ .!portant clinically because%

a+ Nu!erous ducts and vessels traverse it

b+ Carcino!a usually located here

D%ct of irs%ng 2Main pancreatic d%ct3

DISEASES OF T'EDISEASES OF T'E

P A N C R E A SP A N C R E A S

F ,ongenital anomalies,ongenital anomalies , Agenesis& hypoplasia& ectopia& d%ct anomaliesAgenesis& hypoplasia& ectopia& d%ct anomalies

F Exocrine pancreasExocrine pancreas

, ,ystic fibrosis,ystic fibrosis , Ac%te pancreatitisAc%te pancreatitis

, ,hronic pancreatitis,hronic pancreatitis

, ,arcinoma of the pancreas,arcinoma of the pancreas

F Endocrine pancreasEndocrine pancreas , Diabetes mellit%sDiabetes mellit%s

, +slet cell t%mors+slet cell t%mors

.V+ ancreatic /isorders

(+ ancreatitis% diagnosis depends on

clinical evidence

1+ 0sually secondary to biliary tract

disease

2+ $urgery o# biliary tract or sto!ac alcoholis! are other causes

DISEASES OF T'E EOCRINE PANCREASDISEASES OF T'E EOCRINE PANCREAS

ACUTE PANCREATITISACUTE PANCREATITISF PathologyPathology

, > basic alterations> basic alterationsF #3 Proteolytic destr%ction of pancreatic s%bstance#3 Proteolytic destr%ction of pancreatic s%bstanceF 53 *ecrosis of blood vessels @ interstitial53 *ecrosis of blood vessels @ interstitial

hemorrhagehemorrhageF <3 -at necrosis by lipolytic en'ymes<3 -at necrosis by lipolytic en'ymesF >3 Associated ac%te inflammatory reaction>3 Associated ac%te inflammatory reaction

, Pathologic lesionsPathologic lesionsF a. Ac%te pancreatic necrosisa. Ac%te pancreatic necrosis

F b. Ac%te hemorrhagic pancreatitisb. Ac%te hemorrhagic pancreatitisF c. S%pp%rative peritonitisc. S%pp%rative peritonitisF d. Pancreatic pse%docystsd. Pancreatic pse%docysts

ACUTE PANCREATITISACUTE PANCREATITISF PathogenesisPathogenesis

, A%todigestion of pancreatic tiss%e by inappropriatelyA%todigestion of pancreatic tiss%e by inappropriatelyactivated pancreatic en'ymesactivated pancreatic en'ymes

, TrypsinTrypsin has a ma8or rolehas a ma8or role

F a. Activates other proen'ymesa. Activates other proen'ymes 2proelastase2proelastase &&prophospholipase 3prophospholipase 3

F b. ,onverts pre7alli7rein to 7alli7rein 2inin system3b. ,onverts pre7alli7rein to 7alli7rein 2inin system3F c. Hageman factor is activatedc. Hageman factor is activated

, Mechanisms of pancreatic en'yme activationMechanisms of pancreatic en'yme activation

F #3 Pancreatic d%ct obstr%ction#3 Pancreatic d%ct obstr%ctionF 53 Primary acinar cell in8%ry53 Primary acinar cell in8%ryF <3 Defective intracell%lar transport of proen'ymes<3 Defective intracell%lar transport of proen'ymes

4ithin acinar cells4ithin acinar cells

ACUTE PANCREATITISACUTE PANCREATITIS

F ,linical feat%res,linical feat%res , Abdominal pain is the cardinal manifestationAbdominal pain is the cardinal manifestation

epigastric& radiating to bac7& variable in severityepigastric& radiating to bac7& variable in severity

, Shoc7 d%e to pancreatic hemorrhage @ releaseShoc7 d%e to pancreatic hemorrhage @ releaseof vasodilatory agents 26 @ P;s3of vasodilatory agents 26 @ P;s3

F LabLab ↑

ser%m amylase and lipaseOser%m amylase and lipaseO↓

,aO,aO

bilir%bin&bilir%bin&↑

gl%cose @ glycos%riagl%cose @ glycos%ria

F ,T scan,T scan inflammation& pse%docystsinflammation& pse%docystsF PxPx severe cases have high mortality rate 25"(>"C3severe cases have high mortality rate 25"(>"C3

F Death d%e toDeath d%e to #3 shoc7& 53 secondary abdominal#3 shoc7& 53 secondary abdominalsepsis& <3 ad%lt respiratory distress syndromesepsis& <3 ad%lt respiratory distress syndrome

C'RONIC PANCREATITISC'RONIC PANCREATITIS

F 1epeated bo%ts1epeated bo%ts of mild to moderate pancreaticof mild to moderate pancreaticinflammation& 4ith contin%edinflammation& 4ith contin%ed lossloss of pancreaticof pancreaticparenchyma @ replacement byparenchyma @ replacement by fibro%sfibro%s tiss%etiss%e

F Distinction from ac%te pancreatitisDistinction from ac%te pancreatitis may be diffic%ltOmay be diffic%ltO

distinction is made if there is evidence of previo%sdistinction is made if there is evidence of previo%sattac7sattac7sF Middle(aged men& mostly inMiddle(aged men& mostly in alcoholicsalcoholics b%t may d%eb%t may d%e

to biliary tract disease& hyperlipoproteinemia @to biliary tract disease& hyperlipoproteinemia @hypercalcemiaO no apparent ca%se in !"C of caseshypercalcemiaO no apparent ca%se in !"C of cases

F PathogenesisPathogenesis: , Protein hypersecretion from acinar cellsProtein hypersecretion from acinar cells , Precipitation of proteins forming d%ctal pl%gsPrecipitation of proteins forming d%ctal pl%gs

, Pl%gs enlarge forming laminar aggregatesPl%gs enlarge forming laminar aggregates

C'RONIC PANCREATITISC'RONIC PANCREATITISF PathologyPathology

, Hard organ 4ith dilated d%cts @ calcified concretionsHard organ 4ith dilated d%cts @ calcified concretions , -ibrosis& chronic inflammatory cells& obstr%ction of-ibrosis& chronic inflammatory cells& obstr%ction of

d%cts by protein pl%gsd%cts by protein pl%gs , Extensive atrophy of exocrine glandsExtensive atrophy of exocrine glands , Pse%docystsPse%docysts

F ,linical feat%res,linical feat%res , 1epeated attac7s of abdominal pain or may be silent1epeated attac7s of abdominal pain or may be silent

F DxDx clinical s%spicion& lab @ ,Tclinical s%spicion& lab @ ,T

F PxPx chronic disabling disease d%e to its ma8orchronic disabling disease d%e to its ma8orcomplications pancreatic ins%fficiency @ diabetescomplications pancreatic ins%fficiency @ diabetesmellit%smellit%s

/+ Chronic ancreatitis

1+ organ usually appears as

s!all, atrophic

2+ Contains scattered echoes#ro! calci#ications

&+ ri!ary cause is alcoholis!

E+ /ilation o# ancreatic /uct

1+ $een in acute or chronic

pancreatitis

2+ reuently associated withneoplas! o# pancreas

&+ iliary tract proble!s

+ (bscess or He!orrhagic ancreatitis

1+ $i!ilar in sonographic appearance 2+ He!orrhagic%

a+ *ass with inho!ogeneous te3ture

b+ (cute he!orrhage% sonolucent to

echogenic

c+ CT scan used #or di##erentiation

4+ ancreatic Tu!ors

1+ *alignant tu!ors usually arise

as adenocarcino!as

2+ .n head o# ancreas% $3 a+ ainless 5aundice

b+ (nore3ia

ancreatic Tu!ors, .n head, continued

c+ Nausea

d+ 6eight loss

e+ .ncreased plas!a a!ylase

#+ .ncreased al"aline phosphatase

g+ *ay involve co!pression o#

pancreatic duct, C/

ancreatic Tumors in the %ead

• Tumors in the headmay compress

biliary ducts or

pancreatic ducts

&+ .n ody o# ancreas% $3

a+ 4nawing pain radiating to bac"

b+ ain increases a#ter eating orlying down

c+ 6eight loss, anore3ia

d+ 7arge tu!or !ay co!press.VC, portal vein

ancreatic tu!ors,continued

'+ .n Tail o#

ancreas% $3 a+ O#ten silent until

local !etastasis occurs

b+ *ay !etastasi8e to%

1+ para-aortic ly!phnodes

2+ spleen

9+ .denti#ied by organ enlarge!ent,

subtle echo changes, irregular outline

:+ *etastases to sto!ach, liver ; lungs

are co!!on

<+ O#ten causes dilation o# ducts

H+ ibrocystic /isease

1+ =esult o# cystic #ibrosis

2+ /iagnosed by !ethods other than

ultrasound

.+ ancreaticolithiasis

1+ Characteristic stone echoes in pancreatic

2+ *ay see atrophied pancreatic parenchy!a

&+ (ssociated with chronic alcoholic

pancreatitis'+ Contours o# body, tail show irregularities

ancreatolithiasis, continued

9+ .ncidence slightly higher in head

:+ (ssociated with occult pancreaticcarcino!a

a+ *ass > 2!! dia!eter

b+ $een with dilation o# pancreaticduct or C/

-*,T+/*=D)S-*,T+/* /-

E*D/,1+*E PA*,1EAS

4iabetes

Endocrine unction %

Cells o# the .slet o# 7angerhans

synthesi8e and release hor!ones into

the circulation+

Hor!ones travel through the bloodstrea!to target tissues Aespecially liver and

!uscle)

(t the target cells, hor!ones bind speci#icreceptors and cause cell changes that

control !etabolis!

Pancreatic endocrine cells reg%latecarbohydrate& fat& protein metabolism

– Alpha cells , secrete the hormoneglucagon

– 6eta cells , secrete the hormones insulinand amylin

– Delta cells , secrete the hormones

gastrin and somatostatin – - cells * secrete hormone pancreatic

polypeptide

!nsulin secretion is controlled

through several mechanisms+• ,hemically , high levels of glucose and amino acids

in the blood

• Hormonally , beta cells are sensitive to several

hormones that may inhibit or cause insulin secretion

• *e%rally , stimulation of the parasympathetic

nervous system causes insulin to be secreted.

!nsulin secretion is decreased by+F /ecreased blood glucose

concentrationF .ncreased blood insulin

concentrationF $y!pathetic sti!ulation

!nsulin

• Transported through the blood to target tissues where

it binds to specific receptors

• The binding of insulin to target cells+ – Acts as a biochemical signal to the inside of the cell

• :verall cell metabolism is stimulated

• There is increased glucose uptake into the cell

• $egulation of glucose breakdown within the cell

• $egulation of protein and lipid breakdown within

the cell

• lood glucose is decreased because insulin causes

glucose to leave the bloodstream and enter the

metaboli3ing cells.• Jith the exception of brain liver and erythrocytes

tissues reRuire membrane glucose carriers.

4iabetes mellitus

Historically distinguished by weight‑

loss, e3cessive urination, thirst, hunger

E3cessive urination polyuriaE3cessive thirst polydipsia

E3cessive hunger polyphagia

*odern characteri8ation is by

hyperglyce!ia and other !etabolic

disorders

*odern classi#ications ATable1<+<)

Type 1 or .//* .nsulin /ependent /iabetes‑

*ellitus

Type 2 or

N.//* Non .nsulin /ependent /iabetes‑ ‑

*ellitus

Other Types o# /iabetes *ellitus

4/* 4estational /iabetes *ellitus‑

-linical Manifestations+;l%cose in %rine( ecause when insulin is not present

glucose is not taken up out of the blood at the targetcells.

2o blood glucose is very highly increased increased

glucose filtered and excreted in the urine 7exceeds

transport maximum8

-linical Manifestations+eight loss ( atient eats but nutrients are not taken up

by the cells and?or are not metaboli3ed properly

/smotic di%resis results in fluid loss

oss of body tissue by metabolism of fats and proteins

olyuria, polydipsia, pholyphagia

Detoacidosis

ats and proteins are !etaboli8ed

e3cessively, and byproducts "nown as

"etone bodies are produced+ These are

released to the bloodstrea! and cause%/ecreased pH Aso increased acidity)

Co!pensations #or !etabolic

acidosis (cetone given o## in breath

1+ (d!inister insulin*ay be o# ani!al or hu!an origin

Cannot be given orally

atient !ust !onitor their bloodglucose concentration and

ad!inister insulin with the correct

ti!ing

Treatment

2+ Control diet

Carbohydrates should !a"e up

about 99-:@ o# patientFs totalcalories

ats should !a"e up >&@ o#

patientFs total calories

roteins should !a"e up about 19-

2@ o# patientFs total calories

&+ *onitor e3ercise

=e!e!ber% !uscles are a target tissue o#insulin, and !etaboli8e !uch glucose #or

energy

$o!eti!es e3ercise →irregular bloodglucose levels $o diabetic patients should

be !onitored when they are e3ercising

Other%

ancreatic transplant G so #ar not

success#ul

E3peri!ental therapies G not as

success#ul as hoped

Type ' or )!44M

*ore co!!on than .//*, o#ten

undiagnosed

.t has a slow onset

*ost co!!on in those '@ years,

though children are being diagnosed!ore regularly

*ay be genetic

Obesity is the greatest ris" #actor #orthis disease

(nd is related to increased incidence

in children

N.//* → insulin resistance in target cells

$ee decreased I cell responsiveness →/ecreased insulin secreted by I cells

(lso abnor!al a!ount o# glucagon

secreted

These e##ects !ay be due to%

1+(bnor!ally #unctioning I cells2+ /ecreased I cell !ass,

or a co!bination o# the two

&+ Target cell resistance to insulin

/ue to%/ecreased nu!ber o# insulin receptors

ostreceptor events !ay be responsible

Cells Jburn outK and beco!e insensitive

Overweight, hyperlipide!ia co!!onAbut these are precursors, not

sy!pto!s)

=ecurrent in#ectionsVisual changes, paresthesias, #atigue

-linical manifestations

Treatment

1+ 6eight loss

2+ (ppropriate diet Asee .//* above)&+ $ul#onyl ureas

sti!ulate I cells to increase insulin

secretion

6or"s only when I cells are still

#unctioning

→ (n enhance!ent o# insulinFs e##ect

at target cells'+ E3ercise - pro!otes weight loss

Treatment

-omplications of 4iabetes Mellitus

(cute%

Hypoglyce!ia rapid decrease in plas!aglucose insulin shoc"

Neurogenic responses G probably due

to decreased glucose to

hypothala!us+$y!pto!s include%

Tachycardia, palpitations, tre!or,

pallor

Headache, di88iness, con#usionVisual changes

Treat!ent %

provide glucose A.+V+ or subcutaneous i#unconscious)

Observe #or relapse

Detoacidosis G involves a precipitating event%

.ncreased hor!ones released wL trau!a

increased glucose produced by the bodyFs cellsThis Jantagoni8esK the e##ects o# any glucose

present

(cidLbase i!balanceolyuria, dehydration

Electrolyte disturbances

Hyperventilation ADuss!aul G deep,

gasping)

CN$ e##ects

(cetone on breath

Treat!ent%

‑ low dose insulin

(lso, ad!inister #luids, electrolytes

Chronic Co!plications o# /*

Neuropathies nerve dys#unctions →

slowing o# nerve conduction+ .n these patients, see%

/egeneration o# neurons

atrophy, paresthesias/epression

4+.+ proble!s, as !uscle !otility

decreased $e3ual dys#unction

*icrovascular disease G chronic

diabetes wL i!proper glucose

!etabolis! → thic"ening o# thebase!ent !e!brane o# capillaries,

particularly in the eye and the "idney+

(s the capillary changes in this way, →/ecreased tissue per#usion

$o ische!ia → hypo3ia

.n the eye G the retina is !etabolically uite

active, so hypo3ia here is a big proble!

$o see%=etinal ische!ia→

or!ation o# !icroaneuris!s, he!orrhage,

tissue in#arct, #or!ation o# new vessels,

retinal detach!ent

.n the "idney G diabetes is the !ost

co!!on cause o# end stage renal‑

disease.n5ured glo!eruli

Aglo!erulosclerosis)

.n these patients, see%roteinuria Aprotein is e3creted into

the urine) → 4enerali8ed body

ede!a, hypertension

* l di th l i

*acrovascular disease G atherosclerosis

laue #or!ation increases→

.ncreased ris" o# coronary arterydisease, so increased ris" o#

!yocardial in#arction

#ailure

$tro"e

eripheral vascular disease

why diabetic patients #ace proble!s with their lower legs and

.ncreased ris" o# in#ections

Endoscopic Stenting for

Pancreatic Diseases

ancreatic 2tents

• 2hape – 9eenen * curve multiple

side holes?distal flaps

– 2herman * straight

multiple side holesproximal flap?distal

pigtail

– Modified -otton*eung

stent , 2*shaped with

distal flap

• 2i3e =;B or 10 &r

• ength =;BG1' cm

ancreatic 2tents , 4esign and

Application

-ommon !ndications• Acute pancreatitis

– 4rainage to preventpost #$- pancreatitis

– Assist endoscopictherapy

• apillotomy

• eaks

• Malignancy – 4rainage to relief pain

• -hronic pancreatitis – AdDuvant therapy for

stone and stricture

:ptimal design of stents• 2i3e 7small8

• Material 7soft8 – ess irritation to ductal

epithelium

• Migrate outspontaneously

TechniRue of ancreatic 2tent

lacement • 4eep cannulationwith guide wireacross papilla or

stricture• V ancreaticpapillotomy

• 2tent inserted

over wire andpositioned withpusher

ost*#$- ancreatitis

!ncidence

• Most commoncomplication of#$-

• !ncidence ;*10E 1Esevere 0.1E fatal

• 2ignificant medical?

social?economic andliability problem

ossible causes

• Acinari3ation ,overfilling

•%yperosmolarity ?contrast allergy

• Trauma , guide wire

• -oagulation inDury

• !mpaired drainage frompancreas

• acterial contamination

• ile contamination

Mechanism of ost #$-

ancreatitis• apillary manipulation results in edema and sphincter

spasm obstructing 4 flow leading to intracellular

activation of en3ymes

• !mproving drainage with 4 stent may prevent post

#$- pancreatitis

4 2tenting revents # in

2:4 ts• >0 ts with pancreatic 2:4 after biliary #2T were

randomi3ed to 4 stent or no stent

• ost #$- pancreatitis occurred in

– 10?=G 7'HE8 with @)o stent

– 1?(1 7'.(E8 with @2tent

• ' ts 7BE8 developed # after stent removal

TarnaskyGastroenterol

4 2tenting for %igh $isk atients

• BH high*risk pts+ 2:M or difficult cannulation V #2T were

randomi3ed

• ost #$- pancreatitis occurred in

– 10?=H 7'>E8 with @)o stent 7; mild ' moderate = severe8

– '?=> 7;E8 with @2tent 7mild pancreatitis8

• 4 cannulation failed in '?(0 pts 7;E8

Fazel GIE 2003

!s 4 2tent )ecessar for # er

!s 4 2tent )ecessary for #very

robably ):T

• !ncreased time and difficulty

• !ncreased risk

• !ncreased cost• $isk of ductal changes from stent irritation

• )eed follow,up to insure stent migration

• May need 'nd procedure for stent removal

Jho Jill enefit from 4 2tenting<

atient &actors

• 2uspected 2:4

• Zoung female• rior post*#$-

pancreatitis

• )ormal serum bilirubin

Technical &actors

• 4ifficult cannulation

• re*cut sphincterotomy

• ancreatic

sphincterotomy

• Ampullectomy• alloon sphincteroplasty

otential $isks of ancreatic

2tenting$isks

• &ailed stent placement

• roximal tip of stent

damages 4• 2tent occlusion

causing pancreatitis

• -hronic ductalchanges

• !nward stent migration

4ilemma

• To consider 4 stent

placement in a @high*

risk patient is a seriousdecision

• !f successful risk of

# is reduced.

• %owever failed attempt

!)-$#A2#2 the risks

alloon 2phincteroplasty / 4ouble

2tents• 4ouble wires

• alloon

sphincteroplast

y• 4ouble stents

for drainage

• 4 stent for

prophylactic

drainage

ancreas 4ivisum

Minor apillotomy with 4 2tenting

-hronic ancreatitis * 2tone /

2tricture

#ndoTherapy for -hronic

ancreatitis

• ess invasive than

surgery

• $esults comparable to

surgery• 2urgery is still possible

after failed endotherapy

• < redicts outcome

after surgery

4ilation?2tenting of ancreatic

2tricture

• 9uide wire 7hydrophilic8across stricture

• 4ilators

– 9raded dilators

– neumatic balloons 7(*H

• 2hort*term pancreatic

stenting to insure drainage

4ilation of Tight 4 2tricture with

2oehendra 2tent $etriever

4ilation of ancreatic 2tricture

via Minor apilla

ti 2t # t ti

ancreatic 2tone #xtraction

• ancreatic sphincterotomy• .0=; guide wire

• 4ilation of orifice?stricture

• 2tone extraction with wire

basket 7e.g. ''8

• < Mechanical lithotripsy

– limitations

• 4 stent for drainage

• #2J to fragment large

7calcified8 stone

2ummary

• 2uccessful pancreatic stenting and drainage

prevents post #$- pancreatitis

• ancreatic stenting is a useful adDunct for assisted

papillotomy• ancreatic stenting provides drainage in patients

undergoing #2J for stone obstruction

• 2tenting helps to improve stricture post dilation and

provides short term pancreatic drainage

PancreaticPancreatic

Neo*!as'Neo*!as'::

T+*es of PancreaticT+*es of Pancreatic

Neo*!as'sNeo*!as's Broadl# s"ea2in$ there are three basicBroadl# s"ea2in$ there are three basic

t#"es9t#"es9

Ducta! adenocarcino'aDucta! adenocarcino'a <D, o!<D, o!

"ancreatic cancers with a - /*#ear"ancreatic cancers with a - /*#earsurvival 6worst o! an# cancersurvival 6worst o! an# cancer

Neuroendocrine tu'orsNeuroendocrine tu'ors a2a islet*a2a islet*

cell tumors rarecell tumors rare C#stic neo"lasms account !or F: o!C#stic neo"lasms account !or F: o!

"ancreatic cancers"ancreatic cancers

C!inica! Scenario ,- C!inica! Scenario ,- Ad i f t&Ad i f t&

Adenocarcino'a of t&e Adenocarcino'a of t&e

PancreasPancreas

@hat are t#"ical s#m"toms o! "ancreatic@hat are t#"ical s#m"toms o! "ancreaticCAGCAG Abdominal "ain*<"ain can su$$est neural Abdominal "ain*<"ain can su$$est neural

"le5us tail lesion unresectabilit# "oor"le5us tail lesion unresectabilit# "oor

"ro$nosis"ro$nosis

Anore5ia Anore5ia

@ei$ht loss@ei$ht loss

>aundice >aundice 7ruritis *<biliar# obstruction7ruritis *<biliar# obstruction

Steatorrhea*<"ancreatic duct obstructionSteatorrhea*<"ancreatic duct obstruction

Ris/ 0actors for PancreaticRis/ 0actors for Pancreatic

Ris/ 0actors for Pancreatics acto s o a c eat c

Cancer1Cancer1

8irml# lin2ed to ci$arette smo2in$8irml# lin2ed to ci$arette smo2in$ o clear dietar# !actorso clear dietar# !actors

Increased BMI associated withIncreased BMI associated with

increased ris2 increased ris2

'ccu"ational e5"osures to amines'ccu"ational e5"osures to amines

6chemistr# hairdressin$ rubber6chemistr# hairdressin$ rubber

wor2 associated with increased ris2 wor2 associated with increased ris2

Adenocarcino'a of t&ePancreas2 CT scanPancreas2 CT scan

CT can con4rm "ancreatic cancer withCT can con4rm "ancreatic cancer witha sensitivit# o! /*D/ 6sensitivit# isa sensitivit# o! /*D/ 6sensitivit# is

limited b# smaller tumor si3elimited b# smaller tumor si3e

'ther than the "resence o! a "ancreatic'ther than the "resence o! a "ancreatic

mass what else can #ou determinemass what else can #ou determine

!rom CT scanG!rom CT scanG 7RESECE o! METASTASES 6alon$ with7RESECE o! METASTASES 6alon$ with

CHRCHR RESECTABILITY RESECTABILITY

Adenocarcino'a of t&ePancreas2 CT scanPancreas2 CT scan

@hat ma2es a "ancreatic mass li2el#@hat ma2es a "ancreatic mass li2el#resectableGresectableG o evidence o! e5tra"ancreatic diseaseo evidence o! e5tra"ancreatic disease

Evidence o! nonobstructive su"eriorEvidence o! nonobstructive su"eriormesenteric*"ortal vein con(uencemesenteric*"ortal vein con(uence

o evidence o! direct tumor e5tension too evidence o! direct tumor e5tension to

the celiac a5is and SMA the celiac a5is and SMA

E?S la"arosco"# are universall# re$ardedE?S la"arosco"# are universall# re$ardedas use!ul ad&uncts to CT not as essentialas use!ul ad&uncts to CT not as essential

howeverhowever

de oca c o a o t ePancreas2 CT scanPancreas2 CT scan

BorderlineJ Resectable lesionsBorderlineJ Resectable lesionsinclude9include9

SMK occlusion o! a short se$mentSMK occlusion o! a short se$ment

6o"en vein "ro5imall# and distall#6o"en vein "ro5imall# and distall# Bod# and tail lesions with celiacBod# and tail lesions with celiac

"ara*aortic nodes in the vicit#"ara*aortic nodes in the vicit#

Tumors brie(# involvin$ the IKCTumors brie(# involvin$ the IKC

ma# be borderlinema# be borderline

Pancreas2 CT scanPancreas2 CT scan

Pancreatic Cancer2Pancreatic Cancer2

Endosco*ic Ad3unctsEndosco*ic Ad3uncts ERC7 can be utili3ed to9ERC7 can be utili3ed to9

detectin$ small tumors not visuali3ed on CT 6irre$ulardetectin$ small tumors not visuali3ed on CT 6irre$ular

solitar# duct stenoses <:cm lon$ abru"t cuto o!solitar# duct stenoses <:cm lon$ abru"t cuto o!

main "ancreatic duct or "anc and bile ductmain "ancreatic duct or "anc and bile duct

obstructionobstruction

"alliatin$ biliar# obstruction"alliatin$ biliar# obstruction

brush c#tolo$# o! the "ancreatic duct has !airbrush c#tolo$# o! the "ancreatic duct has !air

sensitivit# 60, but e5cellent s"eci4cit#sensitivit# 60, but e5cellent s"eci4cit#

E?S can be utili3ed to9E?S can be utili3ed to9 aid in dia$nosis and characteri3ation o! lesionaid in dia$nosis and characteri3ation o! lesion

obtain tissue bio"s#N ma# be associated with lowerobtain tissue bio"s#N ma# be associated with lower

ris2 o! "eritoneal seedin$ c=w "ercutaneous a""roachris2 o! "eritoneal seedin$ c=w "ercutaneous a""roach

Seru' Mar/ersSeru' Mar/ers Is there a role !or serum mar2ersG I! soIs there a role !or serum mar2ersG I! so

whatGwhatG CA :D*D is a sial#lated Lewis A blood $rou" anti$enCA :D*D is a sial#lated Lewis A blood $rou" anti$en

commonl# e5"ressed and shed in "ancreatic andcommonl# e5"ressed and shed in "ancreatic and

he"atobiliar# disease not tumor s"eci4che"atobiliar# disease not tumor s"eci4c This anti$en when si$ni4cantl# increased can assist inThis anti$en when si$ni4cantl# increased can assist in

dierentiatin$ between "ancreatic adenocarcinoma anddierentiatin$ between "ancreatic adenocarcinoma and

in(ammator# "ancreatic diseasein(ammator# "ancreatic disease

decrease in serial CA :D*D correlates with survival o!decrease in serial CA :D*D correlates with survival o!

"ancreatic "atients a!ter sur$er# or chemothera"#"ancreatic "atients a!ter sur$er# or chemothera"# 1ebatable as to whether this is use!ul as earl# treatment1ebatable as to whether this is use!ul as earl# treatment

o! recurrences have not been shown to im"roveo! recurrences have not been shown to im"rove

outcomesoutcomes

Neoad3uvant T&era*+ Neoad3uvant T&era*+ This 0,#o !emale has borderlineJThis 0,#o !emale has borderlineJ

resectable !eatures has been stentedresectable !eatures has been stented

to answer obstructive &aundice viato answer obstructive &aundice via

ERC7 with E?S demonstratin$ aERC7 with E?S demonstratin$ a"ositive adenocarcinoma"ositive adenocarcinoma

Is there an# role !or neoad&uvantIs there an# role !or neoad&uvant

thera"# !or this "atientG I! so whatthera"# !or this "atientG I! so whatsort o! re$imen and with whatsort o! re$imen and with what

ob&ectivesGob&ectivesG

Insu!ino'aInsu!ino'a

@hi""leOs Triad9@hi""leOs Triad9 s#m"toms o! h#"o$l#cemia durin$ !astin$ or e5ercises#m"toms o! h#"o$l#cemia durin$ !astin$ or e5ercise

serum $lucose F-/m$=dL durin$ s#m"tomsserum $lucose F-/m$=dL durin$ s#m"toms

relie! o! s#m"toms with administration o! $lucoserelie! o! s#m"toms with administration o! $lucose

1e4nitive test is 0;*hour !ast with1e4nitive test is 0;*hour !ast withmeasurement o! insulin and $lucosemeasurement o! insulin and $lucose

0/ o! "atients develo" s#m"toms and )BF-, within ;-0/ o! "atients develo" s#m"toms and )BF-, within ;-

hourshours

insulin9$lucose ratio <,.- is indicative o! insulinomainsulin9$lucose ratio <,.- is indicative o! insulinoma

Elevated c*"e"tide "roinsulin levels areElevated c*"e"tide "roinsulin levels arecon4rmator# alon$ with screenin$ !orcon4rmator# alon$ with screenin$ !or

antiinsulin antibodies sul!on#lureasantiinsulin antibodies sul!on#lureas

$o4 are insu!ino'as$o4 are insu!ino'as

!oca!i5ed1!oca!i5ed1 on*invasive "reo"erative ima$in$on*invasive "reo"erative ima$in$

studies !ail to locali3e +,*+/ o!studies !ail to locali3e +,*+/ o!

insulinomasinsulinomas

CT=MRI etc. $enerall# reserved b#CT=MRI etc. $enerall# reserved b#most endocrine sur$eons to r=omost endocrine sur$eons to r=o

he"atic metastaseshe"atic metastases

Intrao"erative ?=S and "al"ation areIntrao"erative ?=S and "al"ation arethe )'L1 standard !or 4ndin$ anthe )'L1 standard !or 4ndin$ an

insulinoma D*:,, sensitivit#insulinoma D*:,, sensitivit#

6&at is *ro*er o*eration 6&at is *ro*er o*eration

* * ** * *

for insu!ino'a1for insu!ino'a1

)enerall# wide Pocher maneuver su"erior)enerall# wide Pocher maneuver su"eriorand in!erior "ancreatic border mobili3ationand in!erior "ancreatic border mobili3ation

medial re(ection o! the s"leenmedial re(ection o! the s"leen

Bimanual "al"ation with ?=SBimanual "al"ation with ?=S

Enucleation o! the lesionEnucleation o! the lesion Secretin can assist in identi!#in$ "ancreaticSecretin can assist in identi!#in$ "ancreatic

duct lea2 a!ter enucleation com"letedduct lea2 a!ter enucleation com"leted

@hat about lesion in "ancreatic headG@hat about lesion in "ancreatic headG

eed to monitor $lucose levels Q:/ minuteseed to monitor $lucose levels Q:/ minutes

until lesion outuntil lesion out

LEARNING O%7ECTI8ESLEARNING O%7ECTI8ES

Liver !unction testsLiver !unction tests Kiral %e"atitis Kiral %e"atitis Autoimmune he"atitis Autoimmune he"atitis 7rimar# Biliar#7rimar# Biliar#

CirrhosisCirrhosis 7rimar# Sclerosin$7rimar# Sclerosin$

Cholan$itisCholan$itis %emochromatosis%emochromatosis

@ilsons@ilsons )allstones and)allstones and

cholec#stitischolec#stitis

Com"lications o! end sta$eCom"lications o! end sta$eliver diseaseliver disease

Ascites Ascites SB7SB7 %e"atorenal S#ndrome%e"atorenal S#ndrome

Ence"halo"ath#Ence"halo"ath#

LI8ER 0UNCTION TESTSLI8ER 0UNCTION TESTS

ALT ALT AST 6S)'T AST 6S)'T

ALPALIE 7%'S7%ATASE ALPALIE 7%'S7%ATASE

BILIR?BIBILIR?BI

ALT and ASTALT and AST

ALT and AST ALT and AST

En3#mes !ound in %e"atoc#tesEn3#mes !ound in %e"atoc#tes Released when liver cells dama$edReleased when liver cells dama$ed

ALT is s"eci4c !or liver in&ur# ALT is s"eci4c !or liver in&ur#

AST 6S)'T is also !ound in s2eletal AST 6S)'T is also !ound in s2eletaland cardiac muscleand cardiac muscle

Transa'initis2 9 : ;Transa'initis2 9 : ;

nor'a!nor'a! ALT "redominant ALT "redominant

Chronic %e" B = CChronic %e" B = C Acute A*E EBK CMK Acute A*E EBK CMK Steatosis = Steatohe"Steatosis = Steatohe"

%emochromatosis%emochromatosis Medications = To5insMedications = To5ins Autoimmune %e"atitis Autoimmune %e"atitis Al"ha*:*antitr#"sin Al"ha*:*antitr#"sin @ilsonOs 1isease@ilsonOs 1isease Celiac 1iseaseCeliac 1isease

AST "redominant AST "redominant Alcohol*related liver d3 Alcohol*related liver d3

Steatosis= Steatohe"Steatosis= Steatohe"

CirrhosisCirrhosis

on*he"atic sourceon*he"atic source %emol#sis%emol#sis

M#o"ath#M#o"ath#

Th#roid diseaseTh#roid disease Strenuous e5erciseStrenuous e5ercise

Severe AST # ALT E!ev2Severe AST # ALT E!ev2

<-:; <-:; Acute Kiral %e"atitis Acute Kiral %e"atitis

does not "redictdoes not "redict

outcomeoutcome

Bili < ;, "oorBili < ;, "oor"ro$nosis"ro$nosis

Ischemic %e"atitisIschemic %e"atitis h#"otensionh#"otension

se"sisse"sis hemorrha$ehemorrha$e

Autoimmune %e"atitis Autoimmune %e"atitis @ilsonOs 1isease@ilsonOs 1isease

Acute bile duct obstr Acute bile duct obstr

%e"atic Arter# li$ation%e"atic Arter# li$ation

Budd*Chiari S#ndromeBudd*Chiari S#ndrome

Medications =Medications =

To5insTo5ins

acetamino"henacetamino"hen CCl-CCl-

AL=ALINE AL=ALINE

P$OSP$ATASEP$OSP$ATASE 8ound in he"atoc#tes that line the bile8ound in he"atoc#tes that line the bile

canaliculicanaliculi Level is raised in Biliar# obstructionLevel is raised in Biliar# obstruction

6causes stretch o! the bile canaliculi6causes stretch o! the bile canaliculi

B?T also !ound in B'E and 7LACETA B?T also !ound in B'E and 7LACETA ))T is also !ound in bile canaliculi and))T is also !ound in bile canaliculi and

there!ore can be used in con&unction withthere!ore can be used in con&unction with Al2 7hos !or "redictin$ liver ori$in Al2 7hos !or "redictin$ liver ori$in

B?T ))T can be raised b# man# dru$sB?T ))T can be raised b# man# dru$sincludin$ Alcohol and there!ore nonincludin$ Alcohol and there!ore nons"eci4cs"eci4c

%ILIRU%IN%ILIRU%IN

@ater insoluble "roduct o! heme@ater insoluble "roduct o! hememetabolismmetabolism

Ta2en u" b# liver and con&u$ated toTa2en u" b# liver and con&u$ated to

become water soluble so it can bebecome water soluble so it can bee5creted in bile and into bowel.e5creted in bile and into bowel.

7atient loo2s >aundiced i! bilirubin <;./7atient loo2s >aundiced i! bilirubin <;./

I! "atient is vomitin$ )REE then the#I! "atient is vomitin$ )REE then the#

have bowel obstruction below the level o!have bowel obstruction below the level o!the Am"ulla o! Kater.the Am"ulla o! Kater.

6$AT IS T$E DEAL 6IT$ 6$AT IS T$E DEAL 6IT$DIRECT AND INDIRECTDIRECT AND INDIRECT

DIRECT AND INDIRECTDIRECT AND INDIRECT

%ILIRU%IN1%ILIRU%IN1 7rehe"atic disease 6e$ hemol#sis7rehe"atic disease 6e$ hemol#sis

causes hi$h bilirubin which is noncauses hi$h bilirubin which is non

con&u$ated ie. Indirect !raction hi$hercon&u$ated ie. Indirect !raction hi$her

%e"atic disease causes increased%e"atic disease causes increasedcon&u$ated and uncon&u$ated bilirubincon&u$ated and uncon&u$ated bilirubin

7ost he"atic disease e$. )allstones have7ost he"atic disease e$. )allstones have

increased con&u$ated 6direct bilirubinincreased con&u$ated 6direct bilirubin

and lead to dar2 urine and "ale stool.and lead to dar2 urine and "ale stool.

So t&ese are 'ar/ersSo t&ese are 'ar/ersof !iver disease "utof !iver disease "ut

are t&e+ tests of !iverare t&e+ tests of !iverfunction1function1

NO>NO>

TESTS O0 LI8ERTESTS O0 LI8ER

0UNCTION0UNCTION 7R'T%R'MBI TIME= IR 7R'T%R'MBI TIME= IR ALB?MI ALB?MI

PROT$ROM%INPROT$ROM%IN

TIME)INR TIME)INR Measure o! the Kitamin P de"endentMeasure o! the Kitamin P de"endent

clottin$ !actors ie. II KII IH and H.clottin$ !actors ie. II KII IH and H. The liver is involved in activatin$ KitaminThe liver is involved in activatin$ Kitamin

P. There!ore in liver dama$e these clottin$P. There!ore in liver dama$e these clottin$

!actors cannot be "roduced.!actors cannot be "roduced. Be!ore #ou believe that "rolon$ed IR isBe!ore #ou believe that "rolon$ed IR is

due to liver disease &ust ma2e sure thedue to liver disease &ust ma2e sure the"atient has adeQuate Kitamin P b# $ivin$"atient has adeQuate Kitamin P b# $ivin$

:,m$ sc.:,m$ sc. )ivin$ Kitamin P has no eect on IR i!)ivin$ Kitamin P has no eect on IR i!

"atient has im"aired s#nthetic !unction."atient has im"aired s#nthetic !unction.

AL%UMINAL%UMIN

AL%UMIN AL%UMIN

Albumin has a hal! li!e o! ;: da#s so the Albumin has a hal! li!e o! ;: da#s so thedro" that occurs with he"atic d#s!unctiondro" that occurs with he"atic d#s!unction

does not occur acutel#does not occur acutel#

That said acute illness can cause albuminThat said acute illness can cause albuminto dro" ra"idl# – a "rocess thou$ht to beto dro" ra"idl# – a "rocess thou$ht to be

due to c#to2ines increasin$ the rate o!due to c#to2ines increasin$ the rate o!

albumin metabolismalbumin metabolism

%'@EKER donOt !or$et that low albumin%'@EKER donOt !or$et that low albuminalso occurs in E7%R'TIC s#ndrome soalso occurs in E7%R'TIC s#ndrome so

alwa#s chec2 the urine !or "rotein.alwa#s chec2 the urine !or "rotein.

TYPICAL PATTERNSTYPICAL PATTERNS

%E7AT'CELL?LAR %E7AT'CELL?LAR IncreasedIncreased

transaminasestransaminases

Kiral %e"atitis Kiral %e"atitis

1ru$s=alcohol1ru$s=alcohol

Autoimmune Autoimmune

AS%AS%

%emochromatosis%emochromatosis

C%'LESTATICC%'LESTATIC Increased Al2 7hos andIncreased Al2 7hos and

BilirubinBilirubin

Also ma# cause Also ma# cause

increasedincreased

)allstones)allstones

7rimar# Biliar#7rimar# Biliar#

CirrhosisCirrhosis

Sclerosin$ Cholan$itisSclerosin$ Cholan$itis

7ancreatic C=a7ancreatic C=a

A!co&o!ic Liver DiseaseA!co&o!ic Liver Disease

A!co&o!ic Liver Disease A!co&o!ic Liver Disease

AST < ALT AST < ALT ;9: * +9: ratio;9: * +9: ratio

AST F +,, AST F +,,

@h# the discre"anc#G@h# the discre"anc#G ET'%ET'% ↑↑ AST AST

s#nthesiss#nthesis

Kit B de! inhibits Kit B de! inhibits

ALT ALT

ET'%ET'% Steatosis D,* :,,Steatosis D,* :,,

he"atitis :,* +/he"atitis :,* +/

cirrhosis * ;,cirrhosis * ;,

))T))T

8IRAL $EPATITIS8IRAL $EPATITIS

8IRAL $EPATITIS 8IRAL $EPATITIS

All e5am Questions rel# on #ou All e5am Questions rel# on #ouunderstandin$ that acute in!ectionunderstandin$ that acute in!ection

has I$M antibodies and chronic hashas I$M antibodies and chronic has

I$)I$)

8ira! $e*atitis 8ira! $e*atitis

NoneNoneInterferonInterferon @@InterferonInterferon

Ri&$virinRi&$virin

IFNIFN

L$/ivudineL$/ivudine

NONENONET*er$+T*er$+

NONENONE'5V v$ine'5V v$ine NONENONE 8mmne glo4lin 8mmne glo4lin

e#om4inan !a## e#om4inan !a##

8mmne glo4lin 8mmne glo4lin

8na#ti!ate& !a## 8na#ti!ate& !a##

Pro*+-$3i,Pro*+-$3i,

@@@@@@'CC$ner'CC$ner

8 0 !8 0 !

NoneNone

2 0 !# 2 0 !#

Co//onCo//on

#.8 #.8

Infet ##Infet ##

'e$titi, 0 'e$titi, 0

#.8 0 8 #.8 0 8

Neon$te, #Neon$te, #

Adu-t, 88#Adu-t, 88#

#.8 #.8

NoneNone

C-ini$-C-ini$-

Fu-/in$ntFu-/in$nt

Prore,,ion toProre,,ion to

*roniit+*roniit+

Fe$- or$-Fe$- or$-@@@@@@

@@@@@@

v$ri$&-ev$ri$&-e

P$renter$- @@P$renter$- @@

Perin$t$- @@Perin$t$- @@

Se3u$- @@Se3u$- @@

Fe$- 0 or$-Fe$- 0 or$-Tr$n,/i,,ionTr$n,/i,,ion

AuteAuteAute J in,idiou,Aute J in,idiou,In,idiou,In,idiou,Aute J in,idiou,Aute J in,idiou,AuteAuteOn,etOn,et

9 7ee6,9 7ee6," 0 8! 7ee6," 0 8! 7ee6,B 7ee6,B 7ee6," 0 8! 7ee6," 0 8! 7ee6, " 7ee6," 7ee6,Inu&$tionInu&$tion

*% *% *D *D * * * * * *

$EPATITIS A$EPATITIS A

$EPATITIS A $EPATITIS A

RA KirusRA Kirus 8ecal*oral8ecal*oral Incubation :/*/, da#sIncubation :/*/, da#s

Anti *%e"atitis A I$M "resent durin$ Anti *%e"atitis A I$M "resent durin$acute illness.acute illness. TH=7revention9 Kaccine Immune serumTH=7revention9 Kaccine Immune serum

$lobulin !or contacts$lobulin !or contacts

759 )ood – doesnOt become chronic rarel#759 )ood – doesnOt become chronic rarel#!ulminant liver !ailure.!ulminant liver !ailure.

$EPATITIS %$EPATITIS %

1A Kirus1A Kirus Consists o! sur!ace and coreConsists o! sur!ace and core Core consists o! Core anti$en and e*Core consists o! Core anti$en and e*

anti$enanti$en Most in!ections are subclinical butMost in!ections are subclinical but

can "resent with arthral$iascan "resent with arthral$ias

$lomerulone"hritis urticaria$lomerulone"hritis urticaria 7arenteral or se5ual transmission.7arenteral or se5ual transmission.

$e*atitis % continued$e*atitis % continued

%e"atocellular necrosis occurs due to the bod#Os%e"atocellular necrosis occurs due to the bod#Osreaction to the virus rather than due to the virusreaction to the virus rather than due to the virusitsel! itsel!

There!ore "atients who have a severe illness !romThere!ore "atients who have a severe illness !romhe" B are more li2el# to clear the virus.he" B are more li2el# to clear the virus.

SER'L')Y9SER'L')Y9 Remember Acute in!ection has I$M chronic has I$)Remember Acute in!ection has I$M chronic has I$) Anti Core I$M is "resent durin$ acute "hase Anti Core I$M is "resent durin$ acute "hase Anti Core I$) indicates chronic in!ection. Anti Core I$) indicates chronic in!ection. 7atients with %e" B e A$ have continued active re"lication7atients with %e" B e A$ have continued active re"lication Immuni3ed or "reviousl# e5"osed "eo"le have e$ativeImmuni3ed or "reviousl# e5"osed "eo"le have e$ative

%BsA$ and %BeA$ the# have I$) Anti %B Core and%BsA$ and %BeA$ the# have I$) Anti %B Core and7ositive anti %e" Bs and e.7ositive anti %e" Bs and e.

Cholan$itisCholan$itis %emochromatosis%emochromatosis

@ilsons@ilsons )allstones and)allstones and

Com"lications o! end sta$eCom"lications o! end sta$eliver diseaseliver disease

Ascites Ascites SB7SB7 %e"atorenal S#ndrome%e"atorenal S#ndrome

Ence"halo"ath#Ence"halo"ath#

ALT ALT AST 6S)'T AST 6S)'T

ALPALIE 7%'S7%ATASE ALPALIE 7%'S7%ATASE

BILIR?BIBILIR?BI

ALT and ASTALT and AST

ALT and AST ALT and AST

En3#mes !ound in %e"atoc#tesEn3#mes !ound in %e"atoc#tes Released when liver cells dama$edReleased when liver cells dama$ed

ALT is s"eci4c !or liver in&ur# ALT is s"eci4c !or liver in&ur#

AST 6S)'T is also !ound in s2eletal AST 6S)'T is also !ound in s2eletaland cardiac muscleand cardiac muscle

Transa'initis2 9 : ;Transa'initis2 9 : ;

nor'a!nor'a! ALT "redominant ALT "redominant

Chronic %e" B = CChronic %e" B = C Acute A*E EBK CMK Acute A*E EBK CMK Steatosis = Steatohe"Steatosis = Steatohe"

%emochromatosis%emochromatosis Medications = To5insMedications = To5ins Autoimmune %e"atitis Autoimmune %e"atitis Al"ha*:*antitr#"sin Al"ha*:*antitr#"sin @ilsonOs 1isease@ilsonOs 1isease Celiac 1iseaseCeliac 1isease

AST "redominant AST "redominant Alcohol*related liver d3 Alcohol*related liver d3

Steatosis= Steatohe"Steatosis= Steatohe"

CirrhosisCirrhosis

on*he"atic sourceon*he"atic source %emol#sis%emol#sis

M#o"ath#M#o"ath#

Th#roid diseaseTh#roid disease

Strenuous e5erciseStrenuous e5ercise

Severe AST # ALT E!ev2Severe AST # ALT E!ev2

<-:; <-:; Acute Kiral %e"atitis Acute Kiral %e"atitis

does not "redictdoes not "redict

outcomeoutcome

Bili < ;, "oorBili < ;, "oor"ro$nosis"ro$nosis

Ischemic %e"atitisIschemic %e"atitis h#"otensionh#"otension

se"sisse"sis hemorrha$ehemorrha$e

Autoimmune %e"atitis Autoimmune %e"atitis @ilsonOs 1isease@ilsonOs 1isease

Acute bile duct obstr Acute bile duct obstr

%e"atic Arter# li$ation%e"atic Arter# li$ation

Budd*Chiari S#ndromeBudd*Chiari S#ndrome

Medications =Medications =

To5insTo5ins

acetamino"henacetamino"hen CCl-CCl-

AL=ALINE AL=ALINE

P$OSP$ATASEP$OSP$ATASE

P$OSP$ATASEP$OSP$ATASE 8ound in he"atoc#tes that line the bile8ound in he"atoc#tes that line the bile

canaliculicanaliculi Level is raised in Biliar# obstructionLevel is raised in Biliar# obstruction

6causes stretch o! the bile canaliculi6causes stretch o! the bile canaliculi

B?T also !ound in B'E and 7LACETA B?T also !ound in B'E and 7LACETA ))T is also !ound in bile canaliculi and))T is also !ound in bile canaliculi and

there!ore can be used in con&unction withthere!ore can be used in con&unction with Al2 7hos !or "redictin$ liver ori$in Al2 7hos !or "redictin$ liver ori$in

B?T ))T can be raised b# man# dru$sB?T ))T can be raised b# man# dru$sincludin$ Alcohol and there!ore nonincludin$ Alcohol and there!ore nons"eci4cs"eci4c

%ILIRU%IN%ILIRU%IN

@ater insoluble "roduct o! heme@ater insoluble "roduct o! hememetabolismmetabolism

Ta2en u" b# liver and con&u$ated toTa2en u" b# liver and con&u$ated to

become water soluble so it can bebecome water soluble so it can be

e5creted in bile and into bowel.e5creted in bile and into bowel.

7atient loo2s >aundiced i! bilirubin <;./7atient loo2s >aundiced i! bilirubin <;./

I! "atient is vomitin$ )REE then the#I! "atient is vomitin$ )REE then the#

have bowel obstruction below the level o!have bowel obstruction below the level o!the Am"ulla o! Kater.the Am"ulla o! Kater.

6$AT IS T$E DEAL 6IT$ 6$AT IS T$E DEAL 6IT$DIRECT AND INDIRECTDIRECT AND INDIRECT

DIRECT AND INDIRECT%ILIRU%IN1%ILIRU%IN1

7rehe"atic disease 6e$ hemol#sis7rehe"atic disease 6e$ hemol#siscauses hi$h bilirubin which is noncauses hi$h bilirubin which is non

con&u$ated ie. Indirect !raction hi$hercon&u$ated ie. Indirect !raction hi$her

%e"atic disease causes increased%e"atic disease causes increasedcon&u$ated and uncon&u$ated bilirubincon&u$ated and uncon&u$ated bilirubin

7ost he"atic disease e$. )allstones have7ost he"atic disease e$. )allstones have

increased con&u$ated 6direct bilirubinincreased con&u$ated 6direct bilirubin

and lead to dar2 urine and "ale stool.and lead to dar2 urine and "ale stool.

So t&ese are 'ar/ersSo t&ese are 'ar/ersof !iver disease "utof !iver disease "ut

are t&e+ tests of !iverare t&e+ tests of !iver

function1function1

NO>NO>

TESTS O0 LI8ERTESTS O0 LI8ER

0UNCTION0UNCTION

0UNCTION0UNCTION 7R'T%R'MBI TIME= IR 7R'T%R'MBI TIME= IR ALB?MI ALB?MI

PROT$ROM%INPROT$ROM%IN

TIME)INRTIME)INR

TIME)INR TIME)INR Measure o! the Kitamin P de"endentMeasure o! the Kitamin P de"endent

clottin$ !actors ie. II KII IH and H.clottin$ !actors ie. II KII IH and H. The liver is involved in activatin$ KitaminThe liver is involved in activatin$ Kitamin

P. There!ore in liver dama$e these clottin$P. There!ore in liver dama$e these clottin$

!actors cannot be "roduced.!actors cannot be "roduced. Be!ore #ou believe that "rolon$ed IR isBe!ore #ou believe that "rolon$ed IR is

due to liver disease &ust ma2e sure thedue to liver disease &ust ma2e sure the"atient has adeQuate Kitamin P b# $ivin$"atient has adeQuate Kitamin P b# $ivin$

:,m$ sc.:,m$ sc. )ivin$ Kitamin P has no eect on IR i!)ivin$ Kitamin P has no eect on IR i!

"atient has im"aired s#nthetic !unction."atient has im"aired s#nthetic !unction.

AL%UMIN AL%UMIN

Albumin has a hal! li!e o! ;: da#s so the Albumin has a hal! li!e o! ;: da#s so thedro" that occurs with he"atic d#s!unctiondro" that occurs with he"atic d#s!unction

does not occur acutel#does not occur acutel#

That said acute illness can cause albuminThat said acute illness can cause albumin

to dro" ra"idl# – a "rocess thou$ht to beto dro" ra"idl# – a "rocess thou$ht to be

due to c#to2ines increasin$ the rate o!due to c#to2ines increasin$ the rate o!

albumin metabolismalbumin metabolism

%'@EKER donOt !or$et that low albumin%'@EKER donOt !or$et that low albuminalso occurs in E7%R'TIC s#ndrome soalso occurs in E7%R'TIC s#ndrome so

alwa#s chec2 the urine !or "rotein.alwa#s chec2 the urine !or "rotein.

%E7AT'CELL?LAR %E7AT'CELL?LAR IncreasedIncreased

Kiral %e"atitis Kiral %e"atitis

1ru$s=alcohol1ru$s=alcohol

Autoimmune Autoimmune

AS%AS%

%emochromatosis%emochromatosis

C%'LESTATICC%'LESTATIC Increased Al2 7hos andIncreased Al2 7hos and

BilirubinBilirubin

Also ma# cause Also ma# cause

increasedincreased

)allstones)allstones

7rimar# Biliar#7rimar# Biliar#

CirrhosisCirrhosis

Sclerosin$ Cholan$itisSclerosin$ Cholan$itis 7ancreatic C=a7ancreatic C=a

A!co&o!ic Liver Disease A!co&o!ic Liver Disease

AST < ALT AST < ALT ;9: * +9: ratio;9: * +9: ratio

AST F +,, AST F +,,

@h# the discre"anc#G@h# the discre"anc#G ET'%ET'% ↑↑ AST AST

s#nthesiss#nthesis

Kit B de! inhibits Kit B de! inhibits

ALT ALT

ET'%ET'% Steatosis D,* :,,Steatosis D,* :,,

he"atitis :,* +/he"atitis :,* +/

cirrhosis * ;,cirrhosis * ;,

))T))T

8IRAL $EPATITIS 8IRAL $EPATITIS

All e5am Questions rel# on #ou All e5am Questions rel# on #ouunderstandin$ that acute in!ectionunderstandin$ that acute in!ection

has I$M antibodies and chronic hashas I$M antibodies and chronic has

I$)I$)

$EPATITIS A $EPATITIS A

RA KirusRA Kirus 8ecal*oral8ecal*oral Incubation :/*/, da#sIncubation :/*/, da#s

Anti *%e"atitis A I$M "resent durin$ Anti *%e"atitis A I$M "resent durin$acute illness.acute illness. TH=7revention9 Kaccine Immune serumTH=7revention9 Kaccine Immune serum

$lobulin !or contacts$lobulin !or contacts

759 )ood – doesnOt become chronic rarel#759 )ood – doesnOt become chronic rarel#!ulminant liver !ailure.!ulminant liver !ailure.

1A Kirus1A Kirus Consists o! sur!ace and coreConsists o! sur!ace and core Core consists o! Core anti$en and e*Core consists o! Core anti$en and e*

anti$enanti$en Most in!ections are subclinical butMost in!ections are subclinical but

can "resent with arthral$iascan "resent with arthral$ias

$lomerulone"hritis urticaria$lomerulone"hritis urticaria 7arenteral or se5ual transmission.7arenteral or se5ual transmission.

%e"atocellular necrosis occurs due to the bod#Os%e"atocellular necrosis occurs due to the bod#Osreaction to the virus rather than due to the virusreaction to the virus rather than due to the virusitsel! itsel!

There!ore "atients who have a severe illness !romThere!ore "atients who have a severe illness !romhe" B are more li2el# to clear the virus.he" B are more li2el# to clear the virus.

SER'L')Y9SER'L')Y9 Remember Acute in!ection has I$M chronic has I$)Remember Acute in!ection has I$M chronic has I$) Anti Core I$M is "resent durin$ acute "hase Anti Core I$M is "resent durin$ acute "hase Anti Core I$) indicates chronic in!ection. Anti Core I$) indicates chronic in!ection. 7atients with %e" B e A$ have continued active re"lication7atients with %e" B e A$ have continued active re"lication Immuni3ed or "reviousl# e5"osed "eo"le have e$ativeImmuni3ed or "reviousl# e5"osed "eo"le have e$ative

%BsA$ and %BeA$ the# have I$) Anti %B Core and%BsA$ and %BeA$ the# have I$) Anti %B Core and7ositive anti %e" Bs and e.7ositive anti %e" Bs and e.

Hepat!t! B *t!ge* a*d Serology

Core a*t!ge* HepB"g

- "leo"ap!d e*"loe !ral D

- <*d"e "elllar !((*e repo*e

+ a*t!ge* HepB e g- C!r"lat!*g pept!de e6ported

- 8ar%er &or a"t!e !ral repl!"at ) <+C5<<5=- *ly per!t !* pero* ") "!r"l. D

Sr&a"e g HepB S g- >rote!* &o*d o* e*elope

- !rt e!de*"e o& !*&e"t!o* 'e&ore '!o"he( ∆

- S!g*!&!e <+C5< !(pl!e <+C5<<5=

HB D- Bet !*d!"ator o& !ral repl!"at!o*

- ?ally parallel@ HB e g

Core*t!'ody *t! HepB"

- dete"ted !* a*yo*e $) pre!o e6pore

- doe 5 "o*&er prote"t!!ty

- <g8 - a"te !*&e"t!o* ) lat 3-A (o.

- <g/ - !(pl!e "hro*!" hep B Φ

- pree*t !* $!*do$ per!od

+ *t!'ody *t! HepB e - !*d!"ate a*t!ge* ! "leared ) !r *ot repl!

- de"reae !*&e"t!!ty

Sr&a"e ' *t! HepB S- "o*&er >5+C5<<5=

- !g*!&!e re"oery &ro( HB !*&e"t!o*

*o*-!*&e"t!!ty, a""!*at!o* Φ

Sero-oi$- P$ttern, of Aute 1 C*roni 'e$titi, 5

Serolog!" >atter* o& Hep B <*&.

1. <((*!Eat!o*

2. e(ote <*&e"t!o*---@-

Preore /ut$tion (Meditter$ne$n)

H</H <+C5<<5=<g/@

e"oery &ro( HB !*&e"t!o*@J--<g/@-

1. ale >o!t!e

2. #e l!%ely – !*& ro(ote pat--<g/--

1. "te HB <*&e"t!o*

2. F!*do$ >er!od@J-@J-<g8--

Chro*!" ) #ate a"te HB <*&

#F <+C5<<5=@-<g/-@

Chro*!" HB <*&e"t!o*

H</H <+C5<<5=-@<g/-@

"te HB <*&e"t!o*

H</H <+C5<<5=-@<g8-@

Interret$tion nti-*e'5eA nti-*# nti-*s'5,A

?uestion?uestion

A - #o woman "lans to travel to Me5ico with her A - #o woman "lans to travel to Me5ico with herhusband and :: #ear old child. The !amil# have no 2nownhusband and :: #ear old child. The !amil# have no 2nownhistor# o! liver disease or he"atitis and no members o!histor# o! liver disease or he"atitis and no members o!the !amil# have had immuni3ations !or he"atitis. @hatthe !amil# have had immuni3ations !or he"atitis. @hatimmuni3ations would #ou recommend9immuni3ations would #ou recommend9

A. A. %e"atitis A vaccination !or both "arents and child%e"atitis A vaccination !or both "arents and child

B.B. %e"atitis A Kaccination !or "arents and child and%e"atitis A Kaccination !or "arents and child and%e"atitis B vaccination !or the child%e"atitis B vaccination !or the child

C.C. %e"atitis A and %e"atitis B vaccination !or both "arents%e"atitis A and %e"atitis B vaccination !or both "arentsand the childand the child

1.1. Screen "arents !or "revious %e" A in!ection andScreen "arents !or "revious %e" A in!ection andrecommend %e" A vaccination !or the childrecommend %e" A vaccination !or the child

E.E. Screen all members o! the !amil# !or %e" A and BScreen all members o! the !amil# !or %e" A and Be5"osure.e5"osure.

ANS6ER % ANS6ER %

All children should now $et %e" B. All children should now $et %e" B. vaccination as babies i! the# miss vaccination as babies i! the# miss

this the# should have catch u"this the# should have catch u"

vaccination as ::*:; #ear olds vaccination as ::*:; #ear olds 7revious %e" A in!ection is unli2el#7revious %e" A in!ection is unli2el#

in children and adults not in hi$h ris2in children and adults not in hi$h ris2

"o"ulations there!ore it is sa!e to"o"ulations there!ore it is sa!e to vaccinate without antibod# testin$. vaccinate without antibod# testin$.

?UESTION?UESTION

A -, #o married man with two children was recentl# evaluated !or !ati$ue A -, #o married man with two children was recentl# evaluated !or !ati$ueand elevations o! liver !unction tests and was !ound to have chronic %e"and elevations o! liver !unction tests and was !ound to have chronic %e"B. 7h#sical e5amination reveals a !ew s"ider an$iomata on his chest andB. 7h#sical e5amination reveals a !ew s"ider an$iomata on his chest andu""er e5tremities.u""er e5tremities.

Labs9Labs9 %BsA$%BsA$ 7os7os %BeA$%BeA$ 7os7os %BK 1A %BK 1A D, 6lowD, 6low ALT ALT :/ ?=L:/ ?=L Albumin Albumin +.+. IR IR :./:./ A liver bio"s# is "er!ormed and shows cirrhosis with moderate A liver bio"s# is "er!ormed and shows cirrhosis with moderate

in(ammator# activit#in(ammator# activit# The most a""ro"riate recommendation !or this "atient isThe most a""ro"riate recommendation !or this "atient is

A. A. %e should receive the %e"atitis A Kaccine%e should receive the %e"atitis A KaccineB.B. %is @i!e and Childern should receive the %e"atitis B Kaccine%is @i!e and Childern should receive the %e"atitis B Kaccine

C.C. %e should be treated with Inter!eron Al"ha%e should be treated with Inter!eron Al"ha1.1. All o! the above All o! the above

ANS6ER2 D ANS6ER2 D

All "atients with Liver disease should have the All "atients with Liver disease should have the%e"atitis A vaccine as the# have decreased%e"atitis A vaccine as the# have decreasedhe"atic reserve and the mortalit# o! %e"atitis Ahe"atic reserve and the mortalit# o! %e"atitis Ain a "atient with %e"atitis B is considerabl#in a "atient with %e"atitis B is considerabl#increasedincreased

%ousehold contacts o! "atients with %e"atitis B%ousehold contacts o! "atients with %e"atitis Bshould be vaccinatedshould be vaccinated

7atients with %BeA$ are candidates !or7atients with %BeA$ are candidates !orInter!eron thera"# this is most li2el# to bene4tInter!eron thera"# this is most li2el# to bene4t

"atients with %BK 1A F;,, and evidence o!"atients with %BK 1A F;,, and evidence o!on$oin$ immune mediated liver cell dama$e onon$oin$ immune mediated liver cell dama$e onbio"s#.bio"s#.

$e*atitis C$e*atitis C

RA virusRA virus Blood bourne ie. Transmission !rom IKBlood bourne ie. Transmission !rom IK

dru$ use and trans!usion o! blooddru$ use and trans!usion o! blood"roducts "rior to :DD,."roducts "rior to :DD,.

Can also be transmitted b# snortin$Can also be transmitted b# snortin$cocaine.cocaine.

Se5ual transmission is low.Se5ual transmission is low.

Testin$ involves Anti %CK Antibod# andTestin$ involves Anti %CK Antibod# andthen viral load i! "ositive.then viral load i! "ositive. / o! "atients develo" chronic in!ection./ o! "atients develo" chronic in!ection.

Co'*!ications of $e* CCo'*!ications of $e* C

CirrhosisCirrhosis %e"atocellular carcinoma%e"atocellular carcinoma

Cr#o$lobulinaemiaCr#o$lobulinaemia

7ro"h#ria cutanea tarda7ro"h#ria cutanea tarda

Mana(e'ent of $e* CMana(e'ent of $e* C

Inter!eron al"ha with ribavirin !or Inter!eron al"ha with ribavirin !or to :; months clears virus in a""ro5to :; months clears virus in a""ro5-, o! "atients.-, o! "atients.

There is an al$orithm which is used toThere is an al$orithm which is used todecide who is treated but basicall#decide who is treated but basicall#an#one with %e" C hi$h ALT and lessan#one with %e" C hi$h ALT and lessthan -, #o. I! older than -, shouldthan -, #o. I! older than -, should

have bio"s# 4rst which should at leasthave bio"s# 4rst which should at leastshow "eri"ortal in(ammation orshow "eri"ortal in(ammation or4brosis.4brosis.

Ot&er issues re. $e* COt&er issues re. $e* C

'nce "t with %e" C is cirrhotic their'nce "t with %e" C is cirrhotic theirris2 o! develo"in$ he"atocellular Caris2 o! develo"in$ he"atocellular Ca

is :*- "er #earis :*- "er #ear

Alcohol increases ris2 Alcohol increases ris2

Ot&er vira! &e*atitisOt&er vira! &e*atitis

%e" E9 Acute he"atitis &ust li2e he"%e" E9 Acute he"atitis &ust li2e he" A unless #ou are 7RE)AT in A unless #ou are 7RE)AT in

which case can "ro$ress towhich case can "ro$ress to

!ulminant he"atitis!ulminant he"atitis EBK CMK %er"es viruses can allEBK CMK %er"es viruses can all

cause acute he"atitis es"eciall# incause acute he"atitis es"eciall# in

immunocom"romised.immunocom"romised.

?uestion?uestion

A + #o woman was !ound to be %e" C "ositive months a$o a!ter A + #o woman was !ound to be %e" C "ositive months a$o a!terevaluation !or raised AST. The in!ection was attributed to bloodevaluation !or raised AST. The in!ection was attributed to blood

trans!usions received durin$ a car accident :/ #ears a$o. She wastrans!usions received durin$ a car accident :/ #ears a$o. She was"leased to learn last month that she is "re$nant with her 4rst child."leased to learn last month that she is "re$nant with her 4rst child.

The "h#sical e5amination is within normal limitsThe "h#sical e5amination is within normal limits She would li2e !urther in!ormation concernin$ her "ro$nosis andShe would li2e !urther in!ormation concernin$ her "ro$nosis and

the ris2 o! transmission o! %CK to her husband and her child.the ris2 o! transmission o! %CK to her husband and her child. All o! the !ollowin$ statements about %CK in!ection are true e5ce"t9 All o! the !ollowin$ statements about %CK in!ection are true e5ce"t9

A. A. The chance o! transmission o! %CK to the newborn is low in the /The chance o! transmission o! %CK to the newborn is low in the /

ran$e.ran$e.B.B. Barrier "recautions includin$ sa!e se5 are recommended !or allBarrier "recautions includin$ sa!e se5 are recommended !or all

cou"les in a mono$amous relationshi" because o! hi$h ris2 o!cou"les in a mono$amous relationshi" because o! hi$h ris2 o!transmission to the "artnertransmission to the "artner

C.C. Low level transmission o! %e" C is reco$ni3ed within householdsLow level transmission o! %e" C is reco$ni3ed within households6/*:, and the ris2 !or such transmission should be minimi3ed b#6/*:, and the ris2 !or such transmission should be minimi3ed b#"ractices that avoid blood*blood e5"osure such as sharin$ dental"ractices that avoid blood*blood e5"osure such as sharin$ dental

im"lements and ra3orsim"lements and ra3ors1.1. In "atients with %e" C the chance o! develo"in$ cirrhosis overIn "atients with %e" C the chance o! develo"in$ cirrhosis over

several decades is ;,*+/several decades is ;,*+/

Ans4er % Ans4er %

Maternal*!etal %CK transmission is a""ro5Maternal*!etal %CK transmission is a""ro5/ however i! mother is co*in!ected with/ however i! mother is co*in!ected with%IK then ris2 increases to +,%IK then ris2 increases to +,

Ris2 o! se5ual transmission betweenRis2 o! se5ual transmission between

mono$amous s"ouses is also low a""ro5 /mono$amous s"ouses is also low a""ro5 / Transmission can occur between non*se5ualTransmission can occur between non*se5ual

household contacts there!ore should be toldhousehold contacts there!ore should be toldto avoid sharin$ ra3ors etc.to avoid sharin$ ra3ors etc.

;,*+/ o! "atients with %e" C develo";,*+/ o! "atients with %e" C develo"cirrhosiscirrhosis

T&ree @autoi''uneT&ree @autoi''une

!iver diseases!iver diseases

The# are easil# con!used9The# are easil# con!used9 Autoimmune he"atitis Autoimmune he"atitis

7rimar# Biliar# Cirrhosis7rimar# Biliar# Cirrhosis

7rimar# Sclerosin$ Cholan$itis7rimar# Sclerosin$ Cholan$itis

AUTOIMMUNE AUTOIMMUNE

$EPATITIS$EPATITIS

AA "ositive AA "ositive Anti smooth muscle "ositive Anti smooth muscle "ositive %i$h bilirubin and ALT but normal Al2 7hos 6c!.%i$h bilirubin and ALT but normal Al2 7hos 6c!.

7rimar# biliar# cirrhosis7rimar# biliar# cirrhosis 7resentation9 tiredness anore5ia R? "ain7resentation9 tiredness anore5ia R? "ain

cushin$oid !acies des"ite no e5o$enous steroids.cushin$oid !acies des"ite no e5o$enous steroids.Sti$mata o! liver diseaseSti$mata o! liver disease

7atholo$#9 7iecemeal necrosis with l#m"hoc#te7atholo$#9 7iecemeal necrosis with l#m"hoc#tein4ltrationin4ltration

T59 immunosu"ression liver trans"lantT59 immunosu"ression liver trans"lant Com"lications9 All the com"lications o! chronicCom"lications9 All the com"lications o! chronic

liver diseaseliver disease

Pri'ar+ %i!iar+ Cirr&osisPri'ar+ %i!iar+ Cirr&osis

Increased Al2 "hos and Antimitochondrial "ositiveIncreased Al2 "hos and Antimitochondrial "ositive 1ama$e to intralobular bile ducts b# chronic1ama$e to intralobular bile ducts b# chronic$ranulomatous in(ammation$ranulomatous in(ammation

Associated with other autoimmune diseases 6Th#roid RA Associated with other autoimmune diseases 6Th#roid RAS&o$rens S#stemic SclerosisS&o$rens S#stemic Sclerosis

B. See $ranulomas on B5 not "iecemeal necrosisB. See $ranulomas on B5 not "iecemeal necrosis

?nable to e5crete bile there!ore "resent with?nable to e5crete bile there!ore "resent withmalabsor"tion o! !at soluble vitamins. And with evidence o!malabsor"tion o! !at soluble vitamins. And with evidence o!"ortal h#"ertension."ortal h#"ertension.

7resent with lethar$# itchin$ and increased Al2 7hos in a7resent with lethar$# itchin$ and increased Al2 7hos in amiddlea$ed woman.middlea$ed woman.

Ma# have h#"erli"idaemiaMa# have h#"erli"idaemia Consider in an# "atient with autoimmune diseaseConsider in an# "atient with autoimmune disease

"resentin$ with liver disease."resentin$ with liver disease.

Pri'ar+ Sc!erosin(Pri'ar+ Sc!erosin(

C&o!an(itisC&o!an(itis

Seen in "atients with ?C and %IK Seen in "atients with ?C and %IK In(ammation 4brosis and strictures o! biliar# tree causin$In(ammation 4brosis and strictures o! biliar# tree causin$Beaded biliar# treeJ on ERC7Beaded biliar# treeJ on ERC7

Chronic biliar# obstruction leads to cirrhosisChronic biliar# obstruction leads to cirrhosis 7resentation9 As#m"tomatic hi$h Al2 7hos >aundice7resentation9 As#m"tomatic hi$h Al2 7hos >aundice

"ruritis abdo "ain and !ati$ue"ruritis abdo "ain and !ati$ue

159 %i$h bilirubin and Al2 "hos but E)ATIKE159 %i$h bilirubin and Al2 "hos but E)ATIKEantimitochondrial Ab 6C!. "rimar# biliar# cirrhosisantimitochondrial Ab 6C!. "rimar# biliar# cirrhosis

M$t9 Steroids Cholest#ramine or ursodeo5#cholic acid toM$t9 Steroids Cholest#ramine or ursodeo5#cholic acid totreat the "ruritis and cholestasis but does not aecttreat the "ruritis and cholestasis but does not aectdisease "rocessdisease "rocess

Liver trans"lant !or endsta$e disease but ;, recur.Liver trans"lant !or endsta$e disease but ;, recur. B. 7SC is inde"endent o! activit# o! ?C.B. 7SC is inde"endent o! activit# o! ?C.

6&at does t&is ERCP 6&at does t&is ERCP

s&o41s&o41

NAS$NAS$

on*Alcoholic Steatohe"atitison*Alcoholic Steatohe"atitis Common cause o! elevated liverCommon cause o! elevated liver

!unction tests!unction tests

'!ten "atients have metabolic'!ten "atients have metabolics#ndrome with obesit#s#ndrome with obesit#h#"erli"idemia and diabetesh#"erli"idemia and diabetes

;,*+, "ro$ress to cirrhosis;,*+, "ro$ress to cirrhosis @ei$ht loss control o! li"ids and@ei$ht loss control o! li"ids and

diabetes should reduce "ro$ression.diabetes should reduce "ro$ression.

Genetic Liver diseaseGenetic Liver disease

@ilsons@ilsons %emochromatosis%emochromatosis

Al"ha*:*Antitr#"sin de4cienc# Al"ha*:*Antitr#"sin de4cienc#

$e'oc&ro'atosis$e'oc&ro'atosis

Autosomal recessive Autosomal recessive )ene on Chromosome )ene on Chromosome Increased 8e absor"tion !rom $ut de"ositied in tissuesIncreased 8e absor"tion !rom $ut de"ositied in tissues

causin$ 4brosis and !unctional !ailure.causin$ 4brosis and !unctional !ailure. 7resentation9 BR'E 1IABETESJ but also arthral$ias7resentation9 BR'E 1IABETESJ but also arthral$ias

%e"atos"lenome$all# and sti$mata o! liver disease%e"atos"lenome$all# and sti$mata o! liver disease

testicular atro"h# CC8 due to restrictive cardiom#o"ath#testicular atro"h# CC8 due to restrictive cardiom#o"ath# 159 %i$h 8e and 8erritin low TIBC Low testosterone159 %i$h 8e and 8erritin low TIBC Low testosterone

1iabetic. >oint HRa#s show chondrocalcinosis1iabetic. >oint HRa#s show chondrocalcinosis 1ual ener$# CT scan shows iron overload1ual ener$# CT scan shows iron overload Liver B5 shows 8e stainin$Liver B5 shows 8e stainin$ B. %emochromatosis can be secondar# to B ThalassemiaB. %emochromatosis can be secondar# to B Thalassemia

and re"eated blood trans!usions.and re"eated blood trans!usions.

S/in co!or ofS/in co!or of

?UESTION?UESTION

1urin$ evaluation o! an elevated ALT a -/ #ear old1urin$ evaluation o! an elevated ALT a -/ #ear oldalcoholic man is !ound to have a serum ironalcoholic man is !ound to have a serum ironconcentration o! ;-/m$=dL a total iron bindin$ ca"acit#concentration o! ;-/m$=dL a total iron bindin$ ca"acit#o! ;D, m$=dL - trans!errin saturation and a serumo! ;D, m$=dL - trans!errin saturation and a serum!erritin o! ;:;,n$=mL. The "h#sical e5amination shows!erritin o! ;:;,n$=mL. The "h#sical e5amination showsno evidence o! chronic liver or cardiac diseaseno evidence o! chronic liver or cardiac disease

@hich one o! the !ollowin$ is the most a""ro"riate@hich one o! the !ollowin$ is the most a""ro"riatecourse o! mana$ement !or this "atientGcourse o! mana$ement !or this "atientG

A. A. Bio"s# to ma2e a de4nitive dia$nosisBio"s# to ma2e a de4nitive dia$nosis

B.B. MRI evaluation !or iron overloadMRI evaluation !or iron overload

C.C. @ee2l# "hlebotom#@ee2l# "hlebotom#

1.1. %LA t#"in$%LA t#"in$

Ans4er A Ans4er A

1e4nitive dia$nosis o!1e4nitive dia$nosis o!%emochromatosis reQuires liver%emochromatosis reQuires liver

bio"s# to determine he"atic ironbio"s# to determine he"atic iron

inde5.inde5. I! "ositive the "atients siblin$sI! "ositive the "atients siblin$s

should be screenedshould be screened

6&at is t&is si(n ca!!ed and 6&at is t&is si(n ca!!ed and

4&at is it associated 4it& 1 4&at is it associated 4it& 1

4&at is it associated 4it& 1

6i!sonBs Disease 6i!sonBs Disease

Autosomal Recessive Autosomal Recessive 1eletion on Chromosome :+1eletion on Chromosome :+ 1e!ective intrahe"atic !ormation o! caerulo"lasmin1e!ective intrahe"atic !ormation o! caerulo"lasmin

there!ore !ailure o! biliar# e5cretion and hi$h total bod#there!ore !ailure o! biliar# e5cretion and hi$h total bod#and tissue levels o! co""er.and tissue levels o! co""er.

15 %i$h serum caerulo"lasmin increased urinar# co""er.15 %i$h serum caerulo"lasmin increased urinar# co""er.

7RESETATI'9 Cirrhosis Paiser*8leischer rin$s7RESETATI'9 Cirrhosis Paiser*8leischer rin$sh#"o"arath#roidism arthro"ath# 8anconi s#ndrome 6renalh#"o"arath#roidism arthro"ath# 8anconi s#ndrome 6renaltubular acidosis CS9 7s#chosis e5tra"#ramidaltubular acidosis CS9 7s#chosis e5tra"#ramidals#ndrome mental retardation and sei3ures.s#ndrome mental retardation and sei3ures.

Thin2 o! this in a #oun$ "atient with stran$e neurolo$# andThin2 o! this in a #oun$ "atient with stran$e neurolo$# andliver diseaseliver disease

T59 Co""er chelation with "enicillamine can cure withT59 Co""er chelation with "enicillamine can cure withliver trans"lant B?T the CS seQualae will not resolve.liver trans"lant B?T the CS seQualae will not resolve.

- Antitr+*sin- Antitr+*sinDecienc+Decienc+

Decienc+ Decienc+

T%E A?T'S'MAL 1'MIAT 'ET%E A?T'S'MAL 1'MIAT 'E Severit# o! disease is de"endent on whichSeverit# o! disease is de"endent on which

alleles are aected 6ie which "henot#"ealleles are aected 6ie which "henot#"e

)ene on Chromosome :-)ene on Chromosome :- Intrahe"atic accumulation o!Intrahe"atic accumulation o! UU*:*:

Antitr#"sin causes liver disease and can Antitr#"sin causes liver disease and can

lead to cirrhosislead to cirrhosis

Ma# have Lun$ disease 6em"h#semaMa# have Lun$ disease 6em"h#sema

%udd C&iari S+ndro'e%udd C&iari S+ndro'e

>ust 2now that it is thrombosis o! he"atic veins >ust 2now that it is thrombosis o! he"atic veins Ma# be acute or chronicMa# be acute or chronic Ma# be associated with h#"ercoa$ulable stateMa# be associated with h#"ercoa$ulable state

there!ore must do thrombo"hilia screen. Alsothere!ore must do thrombo"hilia screen. Alsoloo2 !or underl#in$ mali$anac#loo2 !or underl#in$ mali$anac#

Can occur with h#datid c#stsCan occur with h#datid c#sts 7resentation9 ausea Komitin$ Abdo "ain7resentation9 ausea Komitin$ Abdo "ain

Tender he"atome$all# and loss o! he"ato&u$ularTender he"atome$all# and loss o! he"ato&u$ularre(e5re(e5

T59 call a he"atolo$ist9 ma# need TI77S or ma#T59 call a he"atolo$ist9 ma# need TI77S or ma#need "ortocaval or s"lenorenal anastomosis. Ma#need "ortocaval or s"lenorenal anastomosis. Ma#be thrombol#sable. Alwa#s call !or hel".be thrombol#sable. Alwa#s call !or hel".

$e*atoce!!u!ar$e*atoce!!u!arCarcino'aCarcino'a

Carcino'aCa c o a

Ris2 !actors9 %e" B and C CirrhosisRis2 !actors9 %e" B and C Cirrhosiso! an# cause E5"osure too! an# cause E5"osure to

As"er$illus 8lavus to5in As"er$illus 8lavus to5in

Screenin$ – Al"ha!eto"rotein shouldScreenin$ – Al"ha!eto"rotein shouldbe chec2ed annuall# in "atients withbe chec2ed annuall# in "atients with

cirrhosis. eed ?SS i! hi$hcirrhosis. eed ?SS i! hi$h

Less than :/ are resectable atLess than :/ are resectable atdia$nosis.dia$nosis.

To understand (a!!stonesTo understand (a!!stones

You 4rst need to 2now the anatom# You 4rst need to 2now the anatom#o! the biliar# treeo! the biliar# tree

Co'*!ications ofCo'*!ications of(a!!stones(a!!stones

(a sto es(

:.:. In the $all bladder9In the $all bladder9 biliar# colicbiliar# colic Acute and chronic cholec#stitis Acute and chronic cholec#stitis Em"#ema mucoceleEm"#ema mucocele

CarcinomaCarcinoma;.;. In the bile ductsIn the bile ducts

'bstructive >aundice'bstructive >aundice 7ancreatitis7ancreatitis Cholan$itisCholan$itis

+.+. In the )utIn the )ut )allstone ileus)allstone ileus

Acute C&o!ec+stitis Acute C&o!ec+stitis

Stone im"actin$ in nec2 o!Stone im"actin$ in nec2 o!$allbladder$allbladder

Continuous R? "ain vomitin$Continuous R? "ain vomitin$

!ever M?R7%YS SI) 7ositive!ever M?R7%YS SI) 7ositive

?SS9 Thic2ened $all bladder wall?SS9 Thic2ened $all bladder wall %I1A scan9 Bloc2ed c#stic duct%I1A scan9 Bloc2ed c#stic duct T5 7' IK Ab5 anal$esiaT5 7' IK Ab5 anal$esia eeds cholec#stectom# either withineeds cholec#stectom# either within

- hours or wait + months- hours or wait + months

C&ronic C&o!ec+stitisC&ronic C&o!ec+stitis

Ka$ue abdominal "ain (atulence !at Ka$ue abdominal "ain (atulence !atintoleranceintolerance

8air !at !ertile !emales o! !ort#8air !at !ertile !emales o! !ort#

?SS and ERC7 reveal stones. Ma#?SS and ERC7 reveal stones. Ma#need s"hincterotom#need s"hincterotom#

%i!iar+ co!ic%i!iar+ co!ic

R? "ain radiatin$ to bac2 R? "ain radiatin$ to bac2 T5 anal$esia and cholec#stectom#T5 anal$esia and cholec#stectom#

R? "ain ri$ors and >aundice.R? "ain ri$ors and >aundice. eeds IK Ab5eeds IK Ab5

Ga!!stone i!eusGa!!stone i!eus

So rare there is hardl# an# "ointSo rare there is hardl# an# "ointmentionin$ itmentionin$ it

Stone "er!orates )allbladder intoStone "er!orates )allbladder into

duodenum "asses throu$h bowelduodenum "asses throu$h boweland obstructs terminal ileum.and obstructs terminal ileum.

Abdo HR dia$nositic9 Air in CB1 with Abdo HR dia$nositic9 Air in CB1 with

small bowel obstructionsmall bowel obstruction

ERCPERCP

IndicationsIndications

>aundice with dilated ducts on ?SS >aundice with dilated ducts on ?SS Recurrent "ancreatitisRecurrent "ancreatitis 7ost cholec#stectom# "ain 6chec2 !or retained stone7ost cholec#stectom# "ain 6chec2 !or retained stone

Com"licationsCom"lications Acute "ancreatitis Acute "ancreatitis Bleedin$Bleedin$ In!ection – cholan$itisIn!ection – cholan$itis 7er!oration7er!oration

7rocedure7rocedure Sideviewin$ endosco"e used to insert catheter into CB1 andSideviewin$ endosco"e used to insert catheter into CB1 and

in&ect contrast. HRa# screenin$ will then show u" lesions inin&ect contrast. HRa# screenin$ will then show u" lesions inbiliar# treebiliar# tree

Your &ob ie. what "re" does m# "atient need Your &ob ie. what "re" does m# "atient need 7' !or :; hours7' !or :; hours Chec2 clottin$ and "lt countChec2 clottin$ and "lt count 7ro"h#lactic antibiotics as "er endosco"# de"artment7ro"h#lactic antibiotics as "er endosco"# de"artment

"rotocol"rotocol

6&at is t&e si(nFand 4&o 6&at is t&e si(nFand 4&o

4as it na'ed for1 4as it na'ed for1

MedusaMedusa

Sti('ata of !iver diseaseSti('ata of !iver disease

%A1S9%A1S9

7almar Er#thema7almar Er#thema Clubbin$Clubbin$ 1u"#trens1u"#trens Leucon#chiaLeucon#chia 8LA77I) TREM'R 8LA77I) TREM'R

%EET=?77ER B'1Y %EET=?77ER B'1Y

>aundice >aundice

S"ider An$iomataS"ider An$iomata )#naecomastia and scant bod# hair)#naecomastia and scant bod# hair Scratch mar2sScratch mar2s

AB1'ME AB1'ME Ascites Ascites %e"atos"lenome$all#%e"atos"lenome$all#

Ca"ut MedusaCa"ut Medusa %emorrhoids on 7R %emorrhoids on 7R Small testesSmall testes

Cirr&osisCirr&osis

- Sta$es- Sta$es:.:. Liver cell necrosisLiver cell necrosis

;.;. In(ammator# cell in4ltateIn(ammator# cell in4ltate

+.+. 8ibrosis8ibrosis

-.-. odular re$eneration which ma# beodular re$eneration which ma# be

macronodular 6alcohol micronodularmacronodular 6alcohol micronodular

6viral or mi5ed6viral or mi5ed

CAUSES O0 CIRR$OSISCAUSES O0 CIRR$OSIS

Alcohol Alcohol Kiral B=C Kiral B=C Cr#"to$enicCr#"to$enic 7rimar# Biliar# Cirrhosis7rimar# Biliar# Cirrhosis

%emochromatosis%emochromatosis @ilsons@ilsons Al"ha : antitr#"sin de4cienc# Al"ha : antitr#"sin de4cienc# Autoimmune Autoimmune Sclerosin$ Cholan$itisSclerosin$ Cholan$itis

COMPLICATIONSCOMPLICATIONS

7ortal %#"ertension causin$ variceal7ortal %#"ertension causin$ varicealbleedbleed

S"lenome$all# causin$ low "lateletsS"lenome$all# causin$ low "latelets

Ascites Ascites Ence"halo"ath#Ence"halo"ath#

SB7SB7

%e"atorenal s#ndrome%e"atorenal s#ndrome

De'onstrate t&e e;a'inationDe'onstrate t&e e;a'inationnecessar+ to identif+ t&e cause ofnecessar+ to identif+ t&e cause of

a"do'ina! distensiona"do'ina! distension

Ascites Ascites

Accumulation o! !ree (uid in Accumulation o! !ree (uid in"eritoneum"eritoneum

Assessment involves ta2in$ sam"le o! Assessment involves ta2in$ sam"le o!

(uid and chec2in$ albumin content(uid and chec2in$ albumin content SAA)9 Serum Ascites AlbuminSAA)9 Serum Ascites Albumin

)radient)radient

SAA) V Serum Albumin – AscitesSAA) V Serum Albumin – Ascites Albumin Albumin

SAAGSAAG

%I)% ie.%I)% ie. WW:.::.: 7ortal7ortal

h#"ertensionh#"ertension

"resent"resent CirrhosisCirrhosis

Alcoholic he"atitis Alcoholic he"atitis

Con$estive cardiacCon$estive cardiac

!ailure!ailure

%e"atic mets%e"atic mets

L'@ ie F:.:L'@ ie F:.: In(ammator#In(ammator#

causescauses 7eritoneal7eritoneal

carcinomatosiscarcinomatosis 7eritoneal TB7eritoneal TB

7ancreatitis7ancreatitis

SerositisSerositis

Mana(e'ent of AscitesMana(e'ent of Ascites

Salt RestrictSalt Restrict 8luid Restrict8luid Restrict 1iuretics1iuretics

S"ironolactone :,,*;,,m$ =da# to increase urinar#S"ironolactone :,,*;,,m$ =da# to increase urinar#sodium e5cretion. Aim to reduce wei$ht b# :P$ "er da#sodium e5cretion. Aim to reduce wei$ht b# :P$ "er da#

Ma# also need Lasi5Ma# also need Lasi5 Lar$e volume "aracentesisLar$e volume "aracentesis

Should $ive $ Salt "oor Albumin "er liter o! AsciticShould $ive $ Salt "oor Albumin "er liter o! Ascitic(uid removed in "atients with %I)% SAA) otherwise(uid removed in "atients with %I)% SAA) otherwisecan cause "reci"itous !all in B7 and %e"atorenalcan cause "reci"itous !all in B7 and %e"atorenal

s#ndrome.s#ndrome.

8arices and *orta! 8arices and *orta!(astro*at&+ (astro*at&+

8aricea! $e'orr&a(e 8aricea! $e'orr&a(e

Karices develo" at Eso"ha$o$astric &unction due Karices develo" at Eso"ha$o$astric &unction dueto "ortal h#"ertensionto "ortal h#"ertension 8irst bleed has :,*+, mortalit#8irst bleed has :,*+, mortalit# Earl# endosco"# band li$ationEarl# endosco"# band li$ation 'ctreotide decreases the "ortal "ressure and'ctreotide decreases the "ortal "ressure and

ma# sto" the bleedin$ma# sto" the bleedin$ , rebleed within ; #ears, rebleed within ; #ears Bbloc2ers es" 7ro"ranolol reduce "ortalBbloc2ers es" 7ro"ranolol reduce "ortal

"ressure and ma# "revent rebleedin$"ressure and ma# "revent rebleedin$

Serial endosco"# and bandin$ to obliterate theSerial endosco"# and bandin$ to obliterate the varices is also indicated to "revent rebleedin$ varices is also indicated to "revent rebleedin$

S*ontaneous %acteria!S*ontaneous %acteria!PeritonitisPeritonitis

'ccurs in :,*;, o! cirrhotic'ccurs in :,*;, o! cirrhotic"atients with ascites"atients with ascites

Cell count and culture o! ascitic (uidCell count and culture o! ascitic (uid

should be "er!ormed in all "atientsshould be "er!ormed in all "atients 7M cells <;/, is criteria !or7M cells <;/, is criteria !or

dia$nosisdia$nosis

$e*atorena! s+ndro'e$e*atorena! s+ndro'e

Renal !ailure with normal tubularRenal !ailure with normal tubular!unction in "atient with "ortal!unction in "atient with "ortal

h#"ertension.h#"ertension.

Ma# be ""ted b# a$$ressive diuresis.Ma# be ""ted b# a$$ressive diuresis.

Low urine sodium 6but so does "re*Low urine sodium 6but so does "re*

renalrenal

o casts in urineo casts in urine

Renal !unction returns to normal a!terRenal !unction returns to normal a!ter

trans"lant.trans"lant.

Ence*&a!o*at&+ Ence*&a!o*at&+

1ecreased consciousness in "atient with1ecreased consciousness in "atient withsevere liver diseasesevere liver disease Alwa#s loo2 !or cause Alwa#s loo2 !or cause

In!ectionIn!ection Bleedin$Bleedin$

Electrol#te disturbanceElectrol#te disturbance Consti"ationConsti"ation Increased "rotein inta2eIncreased "rotein inta2e

?suall# has increased serum ammonia – which?suall# has increased serum ammonia – which #ou should chec2 althou$h it doesnOt need to #ou should chec2 althou$h it doesnOt need tobe that hi$h !or "t to be ence"halo"athicbe that hi$h !or "t to be ence"halo"athic

T59 LactuloseT59 Lactulose

C&i!dsPu(&C&i!dsPu(&c!assicationc!assication

1onOt learn this &ust 2now the name and the "rinci"le.1onOt learn this &ust 2now the name and the "rinci"le.

It is a scorin$ s#stem used to assess how ris2# sur$er#It is a scorin$ s#stem used to assess how ris2# sur$er#

will be in "ts with liver diseasewill be in "ts with liver disease

Meld scores and Ma#o scores used to assess "ts !orMeld scores and Ma#o scores used to assess "ts !or

liver trans"lant and trans"lant allocationliver trans"lant and trans"lant allocation

Cholan$itisCholan$itis %emochromatosis%emochromatosis @ilsons@ilsons )allstones and)allstones and

Com"lications o! end sta$e liverCom"lications o! end sta$e liver

diseasedisease Ascites Ascites SB7SB7 %e"atorenal S#ndrome%e"atorenal S#ndrome Ence"halo"ath#Ence"halo"ath#

$e*atitis C$e*atitis CTreat'ent inTreat'ent in

Corrections2Corrections2 New Medicine, New Challenges New Medicine, New Challenges

S"encer E""s M1 MBAS"encer E""s M1 MBA

Medical 1irectorMedical 1irectorelaware 1e"artment o! Correctionelaware 1e"artment o! Correction

<$/e, e-*% RN% 'N55C

C*ief% 5ure$u of 'e$-t*$re Servie,De-$7$re De$rt/ent of Corretion

O"3ectivesO"3ectives

1iscuss %e" C In!ection X Current1iscuss %e" C In!ection X CurrentTreatmentTreatment

1escribe %e" C Treatment in Corrections1escribe %e" C Treatment in Corrections

E5"lain ew Medications !or %e" CE5"lain ew Medications !or %e" C 'utline Challen$es 7resented b# ew'utline Challen$es 7resented b# ew

MedicationsMedications

7ro"ose Strate$ies to Address these7ro"ose Strate$ies to Address theseChallen$esChallen$es

$e*atitis C$e*atitis C

%e"atitis C 6%CK is a%e"atitis C 6%CK is a(avivirus related to(avivirus related to Yellow 8ever and @est Yellow 8ever and @estile Kirusile Kirus

Most common chronicMost common chronic

bloodborne in!ectionbloodborne in!ectionin the ?Sin the ?S

Conta$ious liverConta$ious liverdisease causin$ milddisease causin$ mild

illness to seriousillness to seriousli!elon$ illness orli!elon$ illness ordeathdeath

$e* C Trans'ission$e* C Trans'ission

S"read b# blood to blood contact9S"read b# blood to blood contact9 IK dru$ useIK dru$ use Mother to child transmissionMother to child transmission Can be se5uall# transmitted but lessCan be se5uall# transmitted but less

commoncommon Since :DD; screenin$ has limited s"readSince :DD; screenin$ has limited s"read

throu$h trans!usions and trans"lantsthrou$h trans!usions and trans"lants

8or most acute in!ection leads to8or most acute in!ection leads to

chronic in!ectionchronic in!ection There is no vaccine !or %e"atitis CThere is no vaccine !or %e"atitis C

Current $e*atitis CCurrent $e*atitis CTreat'entTreat'ent

7E)*Inter!eron7E)*Inter!eron Increases e5"ression o! "roteins thatIncreases e5"ression o! "roteins that

inter!ere with %e" C viral re"licationinter!ere with %e" C viral re"lication

RibavirinRibavirin Enhances the antiviral eect o!Enhances the antiviral eect o!

inter!eroninter!eron

7recise mechanism o! action uncertain7recise mechanism o! action uncertain

Treatment lasts !or one #earN i!Treatment lasts !or one #earN i!

success!ul induces curesuccess!ul induces cure

Side Eects Current $e* CSide Eects Current $e* CTreat'entTreat'ent

INTER0ERONINTER0ERON % t l i li ti 6i% t l i li ti 6i

INTER0ERONINTER0ERON * %ematolo$ic com"lications 6i.e.* %ematolo$ic com"lications 6i.e.neutro"enia thromboc#to"enia neuro"s#chiatricneutro"enia thromboc#to"enia neuro"s#chiatriccom"lications 6i.e. memor# and concentrationcom"lications 6i.e. memor# and concentrationdisturbances visual disturbances headachesdisturbances visual disturbances headachesde"ression irritabilit# (uli2e s#m"toms metabolicde"ression irritabilit# (uli2e s#m"toms metaboliccom"lications 6i.e. h#"oth#roidismcom"lications 6i.e. h#"oth#roidism

h#"erth#roidism low*$rade !ever $astrointestinalh#"erth#roidism low*$rade !ever $astrointestinalcom"lications 6i.e. nausea vomitin$ wei$ht losscom"lications 6i.e. nausea vomitin$ wei$ht lossdermatolo$ic com"lications 6i.e. alo"ecia anddermatolo$ic com"lications 6i.e. alo"ecia and"ulmonar# com"lications 6i.e. interstitial 4brosis"ulmonar# com"lications 6i.e. interstitial 4brosis

RI%A8IRINRI%A8IRIN * %ematolo$ic com"lications 6i.e.* %ematolo$ic com"lications 6i.e.hemol#tic anemia re"roductive com"lications 6i.e.hemol#tic anemia re"roductive com"lications 6i.e.birth de!ects and metabolic com"lications 6i.e.birth de!ects and metabolic com"lications 6i.e.$out$out

Ne4 $e*atitis CNe4 $e*atitis CTreat'entTreat'ent

81A recentl# a""roved two new "rotease81A recentl# a""roved two new "roteaseinhibitors !or treatment o! %e" Cinhibitors !or treatment o! %e" C Boce"revirBoce"revir Tela"revirTela"revir

Are added to do not re"lace ori$inal thera"# Are added to do not re"lace ori$inal thera"# Indications9Indications9

treatment o! chronic %e" C $enot#"e :treatment o! chronic %e" C $enot#"e : with com"ensated liver disease includin$with com"ensated liver disease includin$

cirrhosiscirrhosis "reviousl# untreated or who have !ailed "revious"reviousl# untreated or who have !ailed "revious

inter!eron and ribavirin thera"#.inter!eron and ribavirin thera"#.

Ne4 $e*atitis CNe4 $e*atitis CTreat'entTreat'ent

In "reviousl# untreated "atients 0D o!In "reviousl# untreated "atients 0D o!those receivin$ tela"revir e5"erienced athose receivin$ tela"revir e5"erienced asustained virolo$ic res"onse 6SKR com"aredsustained virolo$ic res"onse 6SKR com"aredwith less than /, with "e$inter!eron al!awith less than /, with "e$inter!eron al!aand ribavirin treatment alone.and ribavirin treatment alone.

Cure rate !or "atients treated with tela"revirCure rate !or "atients treated with tela"reviracross all studies and across all "atientacross all studies and across all "atient$rou"s was between ;,*-/ hi$her than$rou"s was between ;,*-/ hi$her thancurrent re$imen.current re$imen.

Course o! treatment decreased !rom -Course o! treatment decreased !rom -wee2s to ;- wee2s.wee2s to ;- wee2s.

US F d d D Ad i i t ti (FDA)

C&a!!en(es of Ne4C&a!!en(es of Ne4Treat'entTreat'ent

Cannot be $iven alone or resistance willCannot be $iven alone or resistance willdevelo"develo" Same side eects "lus additional sideSame side eects "lus additional side

eectseects Anemia Anemia eutro"eniaeutro"enia Thromboc#to"eniaThromboc#to"enia Severe RashSevere Rash

Lo$istical Challen$es in the correctionalLo$istical Challen$es in the correctional

environment9environment9 Must be $iven at same time ever# da#Must be $iven at same time ever# da# Must be $iven with !att# !ood 6e.$. ice creamMust be $iven with !att# !ood 6e.$. ice cream

Cost of Ne4 Treat'entCost of Ne4 Treat'ent

Both boce"revir and tela"revir areBoth boce"revir and tela"revir are"riced !or cure"riced !or cure

-/,,, to 0/,,, "er "atient-/,,, to 0/,,, "er "atient

7revalence o! %e" C hi$her in7revalence o! %e" C hi$her in

correctional "atient "o"ulationcorrectional "atient "o"ulation

In 1elaware ,,=0,,, "atients with %e"In 1elaware ,,=0,,, "atients with %e"

Treatment o! entire "o"ulation with newTreatment o! entire "o"ulation with newre$imen would cost u" to ,,,,,,,.re$imen would cost u" to ,,,,,,,.

Entire healthcare bud$et V //,,,,,,.Entire healthcare bud$et V //,,,,,,.

Strate(ies for $e* CStrate(ies for $e* CTreat'entTreat'ent

The 8ederal Bureau o! 7risons usesThe 8ederal Bureau o! 7risons usesthe !ollowin$ criteria !or limitin$the !ollowin$ criteria !or limitin$

%e" C treatment%e" C treatment

7E)*inter!eron contraindicated7E)*inter!eron contraindicated Incarceration "eriod insuicient !orIncarceration "eriod insuicient !or

treatmenttreatment

Inmate has unstable medical or mentalInmate has unstable medical or mental

health conditionhealth condition 7atient re!uses treatment7atient re!uses treatment

Strate(ies for $e* CStrate(ies for $e* CTreat'entTreat'ent

Monitorin$ earl# sta$es o! %e" C ratherMonitorin$ earl# sta$es o! %e" C ratherthan treatment acce"table and occurs inthan treatment acce"table and occurs in

!ree world!ree world

Treatment based on "ro$ression9Treatment based on "ro$ression9

Liver !unction testsLiver !unction tests Liver bio"s#Liver bio"s#

'ther !actors9 a$e co*in!ection with %IK etc.'ther !actors9 a$e co*in!ection with %IK etc.

Monitor "atients with earlier sta$es o!Monitor "atients with earlier sta$es o!

4brosis X sentences under / #ears X4brosis X sentences under / #ears X

coordinate with communit# "roviders !orcoordinate with communit# "roviders !or

"otential treatment"otential treatment

Consensus on Use of Ne4Consensus on Use of Ne4MedicationsMedications

I! 4brosis "ro$ression indicates treatmentI! 4brosis "ro$ression indicates treatment"atients are tried on current thera"# 4rst"atients are tried on current thera"# 4rst

I! thera"# !ound to be !utile at :; wee2sI! thera"# !ound to be !utile at :; wee2s

"atients are tried on new medical"atients are tried on new medical

re$imen "rovided there are nore$imen "rovided there are nocontraindicationscontraindications

As with current "ractice "atients should As with current "ractice "atients should

be involved in the decision to treatbe involved in the decision to treat

whether usin$ old or new re$imenwhether usin$ old or new re$imen

Conc!usionConc!usion

1iscussed %e" C In!ection X Current1iscussed %e" C In!ection X CurrentTreatmentTreatment

1escribed %e" C Treatment in Corrections1escribed %e" C Treatment in Corrections

E5"lained ew Medications !or %e" CE5"lained ew Medications !or %e" C 'utlined Challen$es 7resented b# ew'utlined Challen$es 7resented b# ew

MedicationsMedications

7ro"osed Strate$ies to Address these7ro"osed Strate$ies to Address theseChallen$esChallen$es

$e*atitis C$e*atitis CTreat'ent inTreat'ent in

Corrections2Corrections2 New Medicine, New Challenges New Medicine, New Challenges

S"encer E""s M1 MBAS"encer E""s M1 MBA

Medical 1irectorMedical 1irectorelaware 1e"artment o! Correctionelaware 1e"artment o! Correction

<$/e, e-*% RN

C*ief% 5ure$u of 'e$-t*$re Servie,De-$7$re De$rt/ent of Corretion

Dru tre$t/ent for

*roni *e$titi, 5 I/-e/entin NICE uid$ne

NICE te*no-o+ $r$i,$- uid$ne 9% 824% 82"% 8B4

Ud$ted !##

%ac/(round2%ac/(round2 4&o is t&e (uidance for 4&o is t&e (uidance for

Adults with chronic he"atitis B. Adults with chronic he"atitis B. These recommendations do notThese recommendations do not

a""l# to "eo"le who are alsoa""l# to "eo"le who are also

in!ected with he"atitis C or 1 orin!ected with he"atitis C or 1 or%IK.%IK.

Reco''endations2Reco''endations2*e(interferon a!faHa*e(interferon a!faHa

7e$inter!eron al!a*;a is recommended as7e$inter!eron al!a*;a is recommended asan o"tion !or the initial treatment o!an o"tion !or the initial treatment o!

adults with chronic he"atitis B 6%BeA$*adults with chronic he"atitis B 6%BeA$*

"ositive or %BeA$*ne$ative."ositive or %BeA$*ne$ative.

1ru$ treatment with "e$inter!eron al!a*1ru$ treatment with "e$inter!eron al!a*

;a or ade!ovir di"ivo5il should be initiated;a or ade!ovir di"ivo5il should be initiated

onl# b# an a""ro"riatel# Quali4edonl# b# an a""ro"riatel# Quali4ed

healthcare "ro!essional with e5"ertise inhealthcare "ro!essional with e5"ertise inthe mana$ement o! viral he"atitis.the mana$ement o! viral he"atitis.

Reco''endations2Reco''endations2adefovir di*ivo;i!adefovir di*ivo;i!

Ade!ovir di"ivo5il is recommended as Ade!ovir di"ivo5il is recommended asan o"tion i!9an o"tion i!9 treatment with inter!eron al!a ortreatment with inter!eron al!a or

"e$inter!eron al!a*;a has been"e$inter!eron al!a*;a has been

unsuccess!ul orunsuccess!ul or a rela"se occurs a!ter success!ul initiala rela"se occurs a!ter success!ul initial

treatment ortreatment or

treatment with inter!eron al!a ortreatment with inter!eron al!a or"e$inter!eron al!a*;a is "oorl# tolerated"e$inter!eron al!a*;a is "oorl# tolerated

or contraindicated.or contraindicated.

Reco''endations2Reco''endations2adefovir di*ivo;i!adefovir di*ivo;i!

Ade!ovir di"ivo5il should not normall# be Ade!ovir di"ivo5il should not normall# be$iven be!ore treatment with lamivudine.$iven be!ore treatment with lamivudine.

It ma# be used either alone or inIt ma# be used either alone or in

combination with lamivudine when9combination with lamivudine when9 treatment with lamivudine has resulted intreatment with lamivudine has resulted in

viral resistance or viral resistance or

lamivudine resistance is li2el# to occurlamivudine resistance is li2el# to occur

ra"idl# and develo"ment o! lamivudinera"idl# and develo"ment o! lamivudine

resistance is li2el# to have an adverseresistance is li2el# to have an adverse

outcome.outcome.

Reco''endations2 entecavir Reco''endations2 entecavir

Entecavir is recommended as an o"tion !orEntecavir is recommended as an o"tion !or

the treatment o! "eo"le with chronicthe treatment o! "eo"le with chronic

%BeA$*"ositive or %BeA$*ne$ative%BeA$*"ositive or %BeA$*ne$ative

he"atitis B in whom antiviral treatment ishe"atitis B in whom antiviral treatment is

indicated.indicated.

Reco''endations2 te!"ivudineReco''endations2 te!"ivudine

Telbivudine is not recommended !or theTelbivudine is not recommended !or the

treatment o! chronic he"atitis B.treatment o! chronic he"atitis B.

7eo"le currentl# receivin$ telbivudine7eo"le currentl# receivin$ telbivudine

should have the o"tion to continue thera"#should have the o"tion to continue thera"#

until the# and their clinicians consider ituntil the# and their clinicians consider it

a""ro"riate to sto".a""ro"riate to sto".

Reco''endations2 tenofovir Reco''endations2 tenofovir

Teno!ovir diso"ro5il is recommended as anTeno!ovir diso"ro5il is recommended as an

o"tion !or the treatment o! "eo"le witho"tion !or the treatment o! "eo"le with

chronic %BeA$*"ositive or %BeA$*ne$ativechronic %BeA$*"ositive or %BeA$*ne$ative

he"atitis B in whom antiviral treatment ishe"atitis B in whom antiviral treatment is

indicated.indicated.

This does 'T a""l# in "atients who alsoThis does 'T a""l# in "atients who alsohave %e" C %e" 1 or %IK have %e" C %e" 1 or %IK

0or discussion0or discussion

@hat is our local e"idemiolo$#G@hat is our local e"idemiolo$#G %ow are we recordin$ and actin$ u"on%ow are we recordin$ and actin$ u"on

an# use o! telbivudineGan# use o! telbivudineG

@hat data is available to measure use o!@hat data is available to measure use o!

these dru$s locall#Gthese dru$s locall#G

Current andCurrent and

0uture Treat'ent0uture Treat'ent

of C&ronicof C&ronic

$e*atitis C$e*atitis C >ohn Scott M1 MSc >ohn Scott M1 MSc

?niversit# o! @ashin$ton?niversit# o! @ashin$ton

CaseCase

-+ #o Asian woman w= chronic %e" C-+ #o Asian woman w= chronic %e" C)T : %CK RA level o! ; million I?=ml)T : %CK RA level o! ; million I?=ml

ALT /+ IR :., Albumin -.: ALT /+ IR :., Albumin -.:

Liver bio"s#9 $rade ; in(ammationLiver bio"s#9 $rade ; in(ammationsta$e ; 4brosissta$e ; 4brosis

@hat to do ne5tG@hat to do ne5tG Treat now or waitGTreat now or waitG

Out!ineOut!ine

E"idemiolo$#E"idemiolo$# atural %istor#atural %istor# Current Thera"#Current Thera"#

*Eicac#*Eicac#*Side eects*Side eects

*Mechanism o! action*Mechanism o! action

*Pinetics*Pinetics 8uture Thera"#8uture Thera"#

E*ide'io!o(+ E*ide'io!o(+

+.D*-.: million Americans are %CK+.D*-.: million Americans are %CK Ab Ab Ma# be as hi$h as 0 millionMa# be as hi$h as 0 million

;.0*+.; million are chronicall#;.0*+.; million are chronicall#in!ectedin!ected

%i$hest "revalence in +,*/- #o%i$hest "revalence in +,*/- #o

%i$hest "revalence in A!rican%i$hest "revalence in A!rican Americans and %is"anics Americans and %is"anicsCDC. ((< 8 "B(RR

Ris/ 0actors for $C8 Ris/ 0actors for $C8

In&ection dru$ use 6,In&ection dru$ use 6, Blood trans!usion be!ore :DD;Blood trans!usion be!ore :DD; Multi"le se5 "artnersMulti"le se5 "artners

Iatro$enic 6hemodial#sis re*use o!Iatro$enic 6hemodial#sis re*use o! vials etc vials etc Intranasal cocaineIntranasal cocaine

7iercin$ tattooin$ scari4cation7iercin$ tattooin$ scari4cation ?n2nown 6:,?n2nown 6:,

Evo!ution of t&era*+ forEvo!ution of t&era*+ for$C8 $C8

8#, /id#,

6&at is Pe(+!ation1 6&at is Pe(+!ation1

Covalent attachment o!Covalent attachment o!"ol#ethelene $l#col to "e"tide"ol#ethelene $l#col to "e"tide Increases h#drod#namic si3eIncreases h#drod#namic si3e 7rolon$ed circulation7rolon$ed circulation

dela#ed renal clearancedela#ed renal clearance 7e$Intron 6:;2d Scherin$7e$Intron 6:;2d Scherin$

7e$as#s 6-,2d Roche7e$as#s 6-,2d Roche En3on "harmaceuticalEn3on "harmaceutical

Adenosine deaminase Adenosine deaminase 'thers9 eulasta 6)CS8'thers9 eulasta 6)CS8

do5orubicindo5orubicin

Side Eects ofSide Eects ofPe(I0N)Ri"avirinPe(I0N)Ri"avirin

• Dere,,ion r$ninfro/ /i-d to ,uiid$-it+

• Irrit$&i-it+% $re,,ive

&e*$vior

• or,enin of /$ni$• F$tiue

• In,o/ni$

• M+$-i$,% fever% f-u

-i6e ,+/to/,• '$ir -o,,

• C+toeni$,QInterfer

T&e i'*ortance of vira!T&e i'*ortance of vira!/inetics/inetics

=inetics and S8R =inetics and S8R GT - Pe(as+s J R8NKGT - Pe(as+s J R8NK

Time %-" $)A status

Jk ( )eg N' log N' log Any

Jk 1' )eg )eg S' log Any

Jk '( )eg )eg )eg os

S1 J#C $"C ><C 5C

Mec&anis' of Action2Mec&anis' of Action2InterferonInterferon

'CV virion,

Interferon $-f$

IFN reetor,

ISG /RNA

Vir$- RNA

ADAOAS

'CV re-i$tive

A,,e/&-+

'CV virion,

Ad$ted fro/

'oofn$-e <. NE<M !##9

$tiv$te,$ntivir$-

RNA,e,

in$tiv$t

e, vir$-

Ri"avirin Prevention ofRi"avirin Prevention ofRe!a*seRe!a*se

Tre$t/entTre$t/ent Fo--o7uFo--o7u

ee6, of tre$t/entee6, of tre$t/ent

#.#2#.#2

!"!" B!B!9#9#2!2!""4#4# 4949

Continue ri&$virin 76 !"Continue ri&$virin 76 !"

Sto ri&$virin $t 76 !"Sto ri&$virin $t 76 !"

r e - $ , e ( ' C V R N A @ )

$rono5i#i et al., Gastroenterology 2006;131:100-' sli&e #ortesy of /( a5lotsy$rono5i#i et al., Gastroenterology 2006;131:100-' sli&e #ortesy of /( a5lotsy

Ri"avirinBs Antivira!Ri"avirinBs Antivira!Mec&anis'sMec&anis's

1irect inhibition o! %CK RA*de"endent1irect inhibition o! %CK RA*de"endentRA "ol#merase GRA "ol#merase G

1e"letion o! intracellular )T7 "ools1e"letion o! intracellular )T7 "ools 'ia'ia IM71% inhibition GIM71% inhibition G

RA muta$enesis leadin$ to [errorRA muta$enesis leadin$ to [errorcatastro"he[ Gcatastro"he[ G

Ri"avirin Antivira!Ri"avirin Antivira!Mec&anis'sMec&anis's

!2OASPR

S-ide ourte,+ <M P$7-ot,6+

0uture T&era*ies0uture T&era*ies

Comin$ soon 6;,::GComin$ soon 6;,::G 7otent7otent

Ra"id antiviral resistance i! used b#Ra"id antiviral resistance i! used b#

itsel! itsel! More side eectsMore side eects

$C8 Life C+c!e2 =e+$C8 Life C+c!e2 =e+0eatures0eatures

Multi"le "roteins mediate %CK entr#9Multi"le "roteins mediate %CK entr#9

C1: Scaven$er Rece"tor B: Claudin : 'ccludin Ker#C1: Scaven$er Rece"tor B: Claudin : 'ccludin Ker#Low 1ensit# Li"o"rotein Rece"torLow 1ensit# Li"o"rotein Rece"tor

In"ut %CK RA is translated a "ol#"rotein is !ormedIn"ut %CK RA is translated a "ol#"rotein is !ormedand individual viral "roteins are released !romand individual viral "roteins are released !rom"ol#"rotein b# cellular and viral "roteases"ol#"rotein b# cellular and viral "roteases

%CK "roteins associate with endo"lasmic reticulum%CK "roteins associate with endo"lasmic reticulummembranes the site o! %CK re"licationmembranes the site o! %CK re"lication

Kirion assembl# occurs at li"id dro"lets Kirion assembl# occurs at li"id dro"lets %CK leaves the cell b# hitchin$ a ride on the%CK leaves the cell b# hitchin$ a ride on the

a"oli"o"rotein B secretion "athwa#a"oli"o"rotein B secretion "athwa#

%CK li!e c#cle is intimatel# tied with li"id metabolism%CK li!e c#cle is intimatel# tied with li"id metabolism

$C8 8aria"i!it+ $C8 8aria"i!it+

RA virus R1R7 lac2s "roo!*readin$RA virus R1R7 lac2s "roo!*readin$!unction!unction Mutations arise durin$ re"licationMutations arise durin$ re"lication

are not correctedare not corrected

)enot#"es)enot#"es $eneticall# diver$ent %CK isolates that can$eneticall# diver$ent %CK isolates that can

be $rou"ed "h#lo$eneticall#be $rou"ed "h#lo$eneticall#

uasis"eciesuasis"ecies

%i$hl# related #et $eneticall# distinct viruses%i$hl# related #et $eneticall# distinct viruses

Dru( Deve!o*'entDru( Deve!o*'entis NOT Eas+ is NOT Eas+

-one for ever+ 8%### dru, /$6e, it into *u/$n,

-One in 2 reeive FDA $rov$-

Vir$- entr+ in*i&itor,Vir$- entr+ in*i&itor,'e$titi, C i//uno-o&u-in 'CI)'e$titi, C i//uno-o&u-in 'CI)'CVA& 9 $nd A& 92 (/ono-on$- A&)'CVA& 9 $nd A& 92 (/ono-on$- A&)

'CV RNA tr$n,-$tion in*i&itor,'CV RNA tr$n,-$tion in*i&itor, ISIS 8"#4 ($nti,en,e)ISIS 8"#4 ($nti,en,e)

P*$,e of Deve-o/entP*$,e of Deve-o/ent

Pre-ini$-Pre-ini$- II IIII IIIIII IVIV

'CV Dru Deve-o/ent

AVI 0 "#92 ($nti,en,e)AVI 0 "#92 ($nti,en,e)'et$:+/e (ri&o:+/e)'et$:+/e (ri&o:+/e)VG"8#C (,/$-- /o-eu-e IRES in*i&itor)VG"8#C (,/$-- /o-eu-e IRES in*i&itor)TT #44 (,iRNA)TT #44 (,iRNA)

Po,ttr$n,-$tion$- roe,,in in*i&itor,Po,ttr$n,-$tion$- roe,,in in*i&itor, ="3- serine +roteinase inhi4itors ="3- serine +roteinase inhi4itors

5ILN !#985ILN !#98ITMN 88ITMN 88V2#V2#SC' 2#4#4"SC' 2#4#4"AC'#9JGS84!AC'#9JGS84!

'CV re-i$tion in*i&itor,'CV re-i$tion in*i&itor, =" +olymerase inhi4itors =" +olymerase inhi4itors

M#9#M#9#'CVB9'CVB9R89!9R89!9<T##4<T##4NM!4NM!4TL !8!2TL !8!2

y#lo+hilin inhi4itorsy#lo+hilin inhi4itorsDE5IO#!2DE5IO#!2NIM 88NIM 88

=" inhi4itors =" inhi4itorsA48% A9A48% A9 *eli#ase inhi4itors *eli#ase inhi4itors

U994U994Reo/&in$nt A& fr$/ent,Reo/&in$nt A& fr$/ent,

Viru, $,,e/&-+ $nd re-e$,e in*i&itor,Viru, $,,e/&-+ $nd re-e$,e in*i&itor,UT!485 (i/ino,u$r-uo,id$,e in*i&itor)UT!485 (i/ino,u$r-uo,id$,e in*i&itor)Ce-o,ivir (-uo,id$,e in*i&itor)Ce-o,ivir (-uo,id$,e in*i&itor)

$a5lotsy /(, he!alie> ", (#*t#hison /G, Gastroenterology 200);132:19)9-9'

$C8 Lifec+c!e$C8 Lifec+c!e

NS Protease Tar(etsNS Protease Tar(ets

Serine rotein$,e

$t$-+ti ,ite

$a5lotsy /(, he!alie> ", (#*t#hison /G, Gastroenterology 200);132:19)9-9'

NS Protease In&i"itorsNS Protease In&i"itors$avin( Reac&ed C!inica!$avin( Reac&ed C!inica!

D !D !

Deve!o*'entDeve!o*'ent 7e"tidomimetic inhibitors7e"tidomimetic inhibitors

BIL ;,: 6Boehrin$er*In$elheimBIL ;,: 6Boehrin$er*In$elheim

Tela"revir 6KHD/, Kerte5 X TibotecTela"revir 6KHD/, Kerte5 X Tibotec Boce"revir 6SC%/,+,+- Scherin$*7lou$hBoce"revir 6SC%/,+,+- Scherin$*7lou$h

TMC -+/+/, 6TibotecTMC -+/+/, 6Tibotec

ITM*:D: 6InterMuneITM*:D: 6InterMune

MP*0,,D 6Merc2MP*0,,D 6Merc2 BI ;,:++/ 6Boehrin$er*In$elheimBI ;,:++/ 6Boehrin$er*In$elheim

one or n o' na on one or n o' na on

4it& Pe(as+s2 Mean 8ira! 4it& Pe(as+s2 Mean 8ira!Res*onseRes*onse

/ / "aseline"aseline

==-->>--44

??--@@"" 11 == 44>> ?? @@ $$ BB11%%

Stuy ime .InStuy ime .Inays/ays/

2 C 7 8 A

C h a n g e f r o m

2 C 7 8 A

C h a n g e f r o m

" a s e l i n e . , o g

" a s e l i n e . , o g 1 % 1 % I 6 D m ,

I 6 D m ,

'egasys E'egasys E!lacebo!lacebo

F-B?%F-B?%

F-B?% E 'eg-I8F-B?% E 'eg-I8

Ree,in6 ' et $-. EASL. Ari- !94#% !##9.Ree,in6 ' et $-. EASL. Ari- !94#% !##9.

Vienn$% Au,tri$. A&,tr$t B4B.Vienn$% Au,tri$. A&,tr$t B4B.S-ide ourte,+ Ro*e Medi$- Aff$ir,

C&aracteri5ation ofC&aracteri5ation ofTe!a*revirResistantTe!a*revirResistant

8ariants 8ariants %i hl iti l l th d%i hl iti l l th d

%i$hl# sensitive clonal method%i$hl# sensitive clonal method 1etect / !reQuenc# o! variants1etect / !reQuenc# o! variants 7er!ormed at da#s - :; :-7er!ormed at da#s - :; :- , seQuences="atient=time "oint, seQuences="atient=time "oint

T2"A V49AJM R822JT 49J822 A829VJT

Lo7 re,i,t$ne 'i* re,i,t$ne

Ad$ted fro/ ieffer T% et $-. !##

T&an/s>T&an/s>

L$rr+ Core+%MD

C*i$ $n% MD

D$ve Gret*%

MD% P*D

Eri$ Coe-

Eri$ Seddi

2e!atocellular2e!atocellularCarcinomaCarcinoma

+mr %ha#at9 2**"+mr %ha#at9 2**"

%e"atocellular carcinoma 6%CC is a "rimar#%e"atocellular carcinoma 6%CC is a "rimar#

li ! th lili ! th li

mali$nanc# o! the liver.mali$nanc# o! the liver. It is now the third leadin$ cause o! cancer deathsIt is now the third leadin$ cause o! cancer deaths

worldwide with over /,,,,, "eo"le aected.worldwide with over /,,,,, "eo"le aected. %e"atitis and e5cessive alcohol are the leadin$%e"atitis and e5cessive alcohol are the leadin$

causes o! %CC.causes o! %CC. 6%e"atitis B or he"atitis C ;, or with cirrhosis6%e"atitis B or he"atitis C ;, or with cirrhosis

6about ,.6about ,. %CC ma# "resent%CC ma# "resent with ri$ht u""er Quadrant "ainwith ri$ht u""er Quadrant "ain

wei$ht loss &aundice bloatin$ !rom ascites andwei$ht loss &aundice bloatin$ !rom ascites and

si$ns o! decom"ensated liver disease.si$ns o! decom"ensated liver disease.

Microsco"icall# there are !ourMicrosco"icall# there are !our

t l i l tt l i l t

c#tolo$ical t#"es9c#tolo$ical t#"es9 4brolamellar4brolamellar "seudo$landular 6adenoid"seudo$landular 6adenoid "leomor"hic 6$iant cell and"leomor"hic 6$iant cell and clear cell.clear cell.

Local e5"ansion intrahe"atic s"readLocal e5"ansion intrahe"atic s"readand distant metastases.and distant metastases.

Serum A87 rise in -,*-.Serum A87 rise in -,*-.

'n CT %CC can have three distinct "atterns o!'n CT %CC can have three distinct "atterns o!

$rowth9$rowth9 A sin$le lar$e tumor A sin$le lar$e tumor

Multi"le tumorsMulti"le tumors

7oorl# de4ned tumor with an in4ltrative $rowth "attern7oorl# de4ned tumor with an in4ltrative $rowth "attern

Dia(nostic ProceduresDia(nostic Procedures

In "atients withIn "atients with lesions less than : cmlesions less than : cm<<<< conservative mana$ement with close<<<< conservative mana$ement with close!ollow u" and!ollow u" and no bio"s# is recommendedno bio"s# is recommended

!ollow*u" and!ollow*u" and no bio"s# is recommendedno bio"s# is recommended.. In "atients withIn "atients with :* to ;*cm lesions a bio"s#:* to ;*cm lesions a bio"s#

should be "er!ormedshould be "er!ormed.. 7atients with lesions7atients with lesions $reater than ; cm$reater than ; cm

cirrhosis characteristic ima$in$ studies andcirrhosis characteristic ima$in$ studies and

elevated A87 values can be mana$edelevated A87 values can be mana$edwithout bio"s#.without bio"s#.

7atients with7atients with lar$e tumors who are notlar$e tumors who are notcandidates !or resection or trans"lantationcandidates !or resection or trans"lantation<<<<<< bio"s# is !reQuentl#<<<<<< bio"s# is !reQuentl# not indicated.not indicated.

Llovet A29 Fuster A9 *rui' AB ,he *arcelona approach: dia!nosis9Llovet A29 Fuster A9 *rui' AB ,he *arcelona approach: dia!nosis9sta!in!9 and treatment o hepatocellular carcinomaB Liver ,ransplBsta!in!9 and treatment o hepatocellular carcinomaB Liver ,ransplBFeb 7;;CD6;E7 "uppl 6:"663-7;BFeb 7;;CD6;E7 "uppl 6:"663-7;B

Im"ortant !eatures that $uideIm"ortant !eatures that $uide

i l dt t t i l d

treatment include9 *treatment include9 * Si3eSi3e

S"read 6sta$eS"read 6sta$e

Involvement o! liver vesselsInvolvement o! liver vessels

7resence o! a tumor ca"sule7resence o! a tumor ca"sule

7resence o! e5trahe"atic7resence o! e5trahe"atic

metastasesmetastases

Kascularit# o! the tumor Kascularit# o! the tumor

A7CC)UICC C!assication A7CC)UICC C!assication

S+ste'S+ste'

C&i!dPu(& scoreC&i!dPu(& score

TheThe C&i!dPu(& score is used to assess t&eC&i!dPu(& score is used to assess t&e

*ro(nosis*ro(nosis of c&ronic !iver disease 'ain!+of c&ronic !iver disease 'ain!+

*ro(nosis*ro(nosis of c&ronic !iver disease 'ain!+of c&ronic !iver disease 'ain!+cirr&osis. To deter'inecirr&osis. To deter'ine treat'ent reQuiredtreat'ent reQuired

and t&eand t&e necessit+ of !iver trans*!antationnecessit+ of !iver trans*!antation..

The score em"lo#s 4ve clinical measures o! liverThe score em"lo#s 4ve clinical measures o! liver

disease. Each measure is scored :*+ with +disease. Each measure is scored :*+ with +indicatin$ most severe deran$ement.indicatin$ most severe deran$ement.

C*roni -iver di,e$,e

i, -$,,ified into

C*i-dPu* -$,, A toC% e/-o+in t*e

$dded ,ore fro/

reatmentD9anagementreatmentD9anagement

Sur$ical resectionSur$ical resection

Liver trans"lantationLiver trans"lantation

7ercutaneous ablation7ercutaneous ablation Alcohol in&ection Alcohol in&ection Radio!reQuenc# ablationRadio!reQuenc# ablation

Transarterial emboli3ation andTransarterial emboli3ation and

chemoemboli3ationchemoemboli3ation

Chemothera"#.Chemothera"#.

QR$di$

QPotenti

Cur$tiv

e QP$--i$tiv

There is no a$reement on a commonThere is no a$reement on a commontreatment strate$# !or "atients withtreatment strate$# !or "atients with%CC worldwide and several "ro"osals%CC worldwide and several "ro"osalshave been "ublished.The three ma&orhave been "ublished.The three ma&or

curative thera"ies resection livercurative thera"ies resection livertrans"lantation and "ercutaneoustrans"lantation and "ercutaneoustreatments com"ete as 4rst*linetreatments com"ete as 4rst*linetreatment o"tion !or small sin$le %CCtreatment o"tion !or small sin$le %CCin "atients with well*"reserved liverin "atients with well*"reserved liver!unction.!unction.

Llovet >M Burrou$hs A Brui5 >. %e"atocellular carcinoma. TheLlovet >M Burrou$hs A Brui5 >. %e"atocellular carcinoma. TheLancet ;,,+N +;9 :D,0–:0.Lancet ;,,+N +;9 :D,0–:0.

7oon RT 8an ST Tsan$ 8% @on$ >. Locore$ional thera"ies !or7oon RT 8an ST Tsan$ 8% @on$ >. Locore$ional thera"ies !orhe"atocellular carcinoma9 a critical review !rom the sur$eon\she"atocellular carcinoma9 a critical review !rom the sur$eon\s"ers"ective. Ann Sur$ ;,,;N ;+/9 -–."ers"ective. Ann Sur$ ;,,;N ;+/9 -–.

Surgery: 7esection an rans!lantationSurgery: 7esection an rans!lantation

Sur$er# is the mainsta# o! %CC treatment and achieve the best outcomes in well*Sur$er# is the mainsta# o! %CC treatment and achieve the best outcomes in well*

selected candidates.selected candidates.

Less than / "atients resectableLess than / "atients resectable

8actors aectin$ resectabilit#98actors aectin$ resectabilit#9

acto s a ect $ esectab t#9acto s a ect $ esectab t#9 Si3eF/cmSi3eF/cm

number o! tumorsnumber o! tumors

involvement o! ma&or structuresinvolvement o! ma&or structures

he"atic !unctionhe"atic !unction

no e5tra*he"atic s"readno e5tra*he"atic s"read

no "ortal h#"ertension ]no "ortal h#"ertension ]

ReQuires e5"erienced sur$ical and su""ortin$ team ]ReQuires e5"erienced sur$ical and su""ortin$ team ]

/ #ear survival ,*0, ]/ #ear survival ,*0, ] + #ear recurrence -/ * ,+ #ear recurrence -/ * ,Llovet >M 8uster > Brui5 >. Intention*to*treat anal#sis o! sur$ical treatment !or earl# he"atocellular carcinoma9 resection versus trans"lantation.Llovet >M 8uster > Brui5 >. Intention*to*treat anal#sis o! sur$ical treatment !or earl# he"atocellular carcinoma9 resection versus trans"lantation.

%e"atolo$# :DDDN +,9 :-+-–-,.%e"atolo$# :DDDN +,9 :-+-–-,.

Ma33a!erro K Re$alia E 1oci R et al. Liver trans"lantation !or the treatment o! small he"atocellular carcinomas in "atients with cirrhosis. En$l >Ma33a!erro K Re$alia E 1oci R et al. Liver trans"lantation !or the treatment o! small he"atocellular carcinomas in "atients with cirrhosis. En$l >

Med :DDN ++-9 D+–D.Med :DDN ++-9 D+–D.

Llovet >M 8uster > Brui5 >. Intention*to*treat anal#sis o! sur$ical treatment !orLlovet >M 8uster > Brui5 >. Intention*to*treat anal#sis o! sur$ical treatment !or

earl# he"atocellular carcinoma9 resection versus trans"lantation. %e"atolo$#earl# he"atocellular carcinoma9 resection versus trans"lantation. %e"atolo$#

:DDDN +,9 :-+-–-,.:DDDN +,9 :-+-–-,.

Ma33a!erro K Re$alia E 1oci R et al. Liver trans"lantation !or the treatment o!Ma33a!erro K Re$alia E 1oci R et al. Liver trans"lantation !or the treatment o!

small he"atocellular carcinomas in "atients with cirrhosis. En$l > Med :DDNsmall he"atocellular carcinomas in "atients with cirrhosis. En$l > Med :DDN

++-9 D+–D.++-9 D+–D.

Trans*!antationTrans*!antation

Milan Criteria 9Milan Criteria 9

Milan Criteria 9Milan Criteria 9 Sin$le %CC ^/ cm orSin$le %CC ^/ cm or ?" to three nodules ^+ cm?" to three nodules ^+ cm o e5tra he"atic s"reado e5tra he"atic s"read About :, Quali!# !or listin$ About :, Quali!# !or listin$

The ma&or drawbac2 o! trans"lantation isThe ma&or drawbac2 o! trans"lantation is The scarcit# o! donors.The scarcit# o! donors. The lon$ waitin$ time.The lon$ waitin$ time.

@hile @aitin$ 9@hile @aitin$ 9

Ad&uvant thera"ies whilst on the waitin$ list Ad&uvant thera"ies whilst on the waitin$ list

are used in most centers to "revent tumorare used in most centers to "revent tumor"ro$ression."ro$ression.

Resection 8sResection 8sTrans*!antaionTrans*!antaion

:+ "t with cirrhosis and %CC:+ "t with cirrhosis and %CC

:+ "t with cirrhosis and %CC:+ "t with cirrhosis and %CC / LT and /+ Resection/ LT and /+ Resection

ChildOs A and BChildOs A and B

rans!lantat

7esection

1, >, ?-year

Survival

4, $4, @= H >, ?$, ?% H

1, >, ?-year

isease free

>, $=, @% H $%, 44, >1 H

Liovet *e$to-o+ 8

Percutaneous Treat'entsPercutaneous Treat'ents

8or "atients who cannot under$o resection.8or "atients who cannot under$o resection. Com"lete res"onses inCom"lete res"onses in more than , o! tumors smallermore than , o! tumors smaller

than + cm in diameterthan + cm in diameter but inbut in /, o! tumors o! +*/ cm in/, o! tumors o! +*/ cm inii

than + cm in diameterthan + cm in diameter but in but in /, o! tumors o! + / cm in/, o! tumors o! + / cm insi3esi3e.. /*#ear survival rates o! -,*,. re"orted in "atients/*#ear survival rates o! -,*,. re"orted in "atients

with small sin$le tumors commonl# F; cm in diameter.with small sin$le tumors commonl# F; cm in diameter. Althou$h these treatments "rovide $ood results the# are Althou$h these treatments "rovide $ood results the# are

unable to achieve res"onse rates and outcomesunable to achieve res"onse rates and outcomescom"arable with sur$ical treatments.com"arable with sur$ical treatments.

Transarterial Emboli3ation and Chemoemboli3ation isTransarterial Emboli3ation and Chemoemboli3ation isrecommended as 4rst line non*curative thera"# !or non*recommended as 4rst line non*curative thera"# !or non*sur$ical "atients with lar$e=multi!ocal %CC who do notsur$ical "atients with lar$e=multi!ocal %CC who do nothave vascular invasion or e5trahe"atic s"read.have vascular invasion or e5trahe"atic s"read.

Sala M Llovet >M Kilana R et al. Initial res"onse to "ercutaneousSala M Llovet >M Kilana R et al. Initial res"onse to "ercutaneousablation "redicts survival in "atients with he"atocellular carcinoma.ablation "redicts survival in "atients with he"atocellular carcinoma.

%e"atolo$# ;,,-N -,9 :+/;–,.%e"atolo$# ;,,-N -,9 :+/;–,. Lencioni R Cioni 1 Crocetti L et al. Earl#*sta$e he"atocellularLencioni R Cioni 1 Crocetti L et al. Earl#*sta$e he"atocellular

carcinoma in "atients with cirrhosis9 lon$*term results o! "ercutaneouscarcinoma in "atients with cirrhosis9 lon$*term results o! "ercutaneousima$e*$uided radio!reQuenc# ablation. Radiolo$# ;,,/N ;+-9 D:–0.ima$e*$uided radio!reQuenc# ablation. Radiolo$# ;,,/N ;+-9 D:–0.

'mata M Tateishi R Yoshida % Shiina S. Treatment o! he"atocellular'mata M Tateishi R Yoshida % Shiina S. Treatment o! he"atocellularcarcinoma b# "ercutaneous tumor ablation methods9 ethanol in&ectioncarcinoma b# "ercutaneous tumor ablation methods9 ethanol in&ectionthera"# and radio!reQuenc# ablation. )astroenterolo$# ;,,-N :;09 S:/D–thera"# and radio!reQuenc# ablation. )astroenterolo$# ;,,-N :;09 S:/D–..

Percutaneous Et&ano! In3ectionPercutaneous Et&ano! In3ection

;,0 "atients with cirrhosis ;,0 "atients with cirrhosis %CC F /%CC F / cm

;,0 "atients with cirrhosis ;,0 "atients with cirrhosis %CC F / cm ]%CC F / cm ] :,, Ethanol:,, Ethanol 8ollow u" was ;/ months8ollow u" was ;/ months

o com"licationso com"lications -.+ sessions "er "atient-.+ sessions "er "atient com"lete necrosis com"lete necrosis : ;+*#ear survival rates9: ;+*#ear survival rates9

D,,+D,,+

Cancer :DD;ND9D;/Cancer :DD;ND9D;/

RadiofreQuenc+ A"!ationRadiofreQuenc+ A"!ation

5EFORE RF

'3I 7A

Com!let H B@ H 7A. /

'3I. /

Com!lete

8ecrosis

H B@ H

'rogres

4%,4H 1?,> H

Survival

?$,@ H $1,1 H

7A.?=/

'3I.@%/

Com!let

8ecrosi

Session

1,= 4,

RFA > More e3en,ive% /oreo/-i$tion% /ore ,eedin.

PEI> More Se,,ion,% -e,, effetive in

Lin et $-. !##"

R$dio-o+ 8? !8#>922

Pa!!iative T&era*iesPa!!iative T&era*ies 7rimar# treatment !or unresectable %CC.7rimar# treatment !or unresectable %CC. Emboli3ation a$ents – usuall# $elatin or micros"heres –Emboli3ation a$ents – usuall# $elatin or micros"heres –

ma# be administered to$ether with selective intra*arterialma# be administered to$ether with selective intra*arterialchemothera"# mi5ed with li"iodol 6chemoemboli3ationchemothera"# mi5ed with li"iodol 6chemoemboli3ation

ma# be administered to$ether with selective intra arterialma# be administered to$ether with selective intra arterialchemothera"# mi5ed with li"iodol 6chemoemboli3ation.chemothera"# mi5ed with li"iodol 6chemoemboli3ation. 1o5orubicin mitom#cin and cis"latin are the commonl#1o5orubicin mitom#cin and cis"latin are the commonl#

used antitumoral dru$s.used antitumoral dru$s. Arterial emboli3ation achieves "artial res"onses in :/* Arterial emboli3ation achieves "artial res"onses in :/*

// o! "atients and si$ni4cantl# dela#s tumour// o! "atients and si$ni4cantl# dela#s tumour

"ro$ression and vascular invasion."ro$ression and vascular invasion.

_ Brui5 > Sala M Llovet >M. Chemoemboli3ation !or he"atocellular_ Brui5 > Sala M Llovet >M. Chemoemboli3ation !or he"atocellularcarcinoma. )astroenterolo$# ;,,-N :;09 S:0D–.carcinoma. )astroenterolo$# ;,,-N :;09 S:0D–.

_ Llovet >M Real MI Montana H et al. Arterial embolisation or_ Llovet >M Real MI Montana H et al. Arterial embolisation orchemoembolisation versus s#m"tomatic treatment in "atients withchemoembolisation versus s#m"tomatic treatment in "atients with

unresectable he"atocellular carcinoma9 a randomised controlled trial.unresectable he"atocellular carcinoma9 a randomised controlled trial.Lancet ;,,;N +/D9 :0+-–D.Lancet ;,,;N +/D9 :0+-–D.

_ Lo CM $an % Tso @P et al. Randomi3ed controlled trial o! transarterial_ Lo CM $an % Tso @P et al. Randomi3ed controlled trial o! transarterialli"iodol chemoemboli3ation !or unresectable he"atocellular carcinoma.li"iodol chemoemboli3ation !or unresectable he"atocellular carcinoma.%e"atolo$# ;,,;N +/9 ::-–0:.%e"atolo$# ;,,;N +/9 ::-–0:.

Transarteria! C&e'oe'"o!i5ationTransarteria! C&e'oe'"o!i5ation

Meta*anal#sis o! 0 randomi3edMeta*anal#sis o! 0 randomi3edt ll d t i lt ll d t i l

Meta*anal#sis o! 0 randomi3edMeta*anal#sis o! 0 randomi3edcontrolled trialscontrolled trials ; #r survival9 -: 6:D*+; #r survival9 -: 6:D*+

Treatment res"onse9 +/ 6:*:Treatment res"onse9 +/ 6:*:

Avera$e no. o! sessions9 :*-./ Avera$e no. o! sessions9 :*-./ Ris2s9Ris2s9

In!ectionIn!ection

Tumor l#sis s#ndromeTumor l#sis s#ndrome

%e"atic !ailure%e"atic !ailure

Llovel > %e aloI;,,+[+09-;DLlovel > %e aloI;,,+[+09-;D

S+ste'ic Treat'entsS+ste'ic Treat'ents

A meta*anal#sis o! seven RCTs com"arin$ A meta*anal#sis o! seven RCTs com"arin$ tamo5i!entamo5i!en

vs. conservative mana$ement vs. conservative mana$ement com"risin$ D com"risin$ D"atients showed neither antitumoral eect nor"atients showed neither antitumoral eect nor

$$ " $ " $"atients showed neither antitumoral eect nor"atients showed neither antitumoral eect norsurvival bene4t o! tamo5i!en. Thus this treatment issurvival bene4t o! tamo5i!en. Thus this treatment isdiscoura$ed in advanced %CC.discoura$ed in advanced %CC.

S#stemic chemothera"# has been tested in nine RCT.S#stemic chemothera"# has been tested in nine RCT.The most active a$ents in vitro and in vivo areThe most active a$ents in vitro and in vivo aredo5orubicin and cis"latindo5orubicin and cis"latin. S#stemic do5orubicin has. S#stemic do5orubicin hasbeen tested in more than :,,, "atients within clinicalbeen tested in more than :,,, "atients within clinicaltrials and "rovides "artial res"onses in around :, o!trials and "rovides "artial res"onses in around :, o!cases without an# evidence o! survival advanta$es .cases without an# evidence o! survival advanta$es .

Llovet >M Brui5 >. S#stematic review o! randomi3ed trials !orLlovet >M Brui5 >. S#stematic review o! randomi3ed trials !orunresectable he"atocellular carcinoma9 chemoemboli3ationunresectable he"atocellular carcinoma9 chemoemboli3ationim"roves survival. %e"atolo$# ;,,+N +09 -;D–-;.im"roves survival. %e"atolo$# ;,,+N +09 -;D–-;.

_ 8on$ Y Pemen# Lawrence T. Cancer o! the liver and biliar#_ 8on$ Y Pemen# Lawrence T. Cancer o! the liver and biliar#tree. In9 1e Kita KT %ellman S Rosenber$ S eds. Cancer9tree. In9 1e Kita KT %ellman S Rosenber$ S eds. Cancer97rinci"les and 7ractices o! 'ncolo$#. 7hiladel"hia ?SA97rinci"les and 7ractices o! 'ncolo$#. 7hiladel"hia ?SA9Li""incott @illiams and @il2ins ;,,:9 ::;–;,-.Li""incott @illiams and @il2ins ;,,:9 ::;–;,-.

_ 7almer 1 %ussain S >ohnson 7. S#stemic thera"ies !or_ 7almer 1 %ussain S >ohnson 7. S#stemic thera"ies !orhe"atocellular carcinoma. E5"ert '"in Investi$ 1ru$s ;,,-N :+9he"atocellular carcinoma. E5"ert '"in Investi$ 1ru$s ;,,-N :+9:///–.:///–.

C&e'ot&era*+ C&e'ot&era*+

7alliative not Curative7alliative not Curative.

R i l 6I i l b h

7alliative not Curative. Re$ional 6Intra*arterial better thatRe$ional 6Intra*arterial better that

s#stemic.s#stemic.

Resistant to man# a$ents.Resistant to man# a$ents.

0o!!o4u*0o!!o4u*

1es"ite o"timal treatment he"atocellular carcinoma1es"ite o"timal treatment he"atocellular carcinoma

continues to have a hi$h recurrence rate. ma&orit# o!continues to have a hi$h recurrence rate. ma&orit# o!h h h

$ & #$ & #which occur within ; #ears.which occur within ; #ears.

Earl# recurrence a!ter resection is associated with aEarl# recurrence a!ter resection is associated with adismal "ro$nosis reducin$ /*#ear survival rates !romdismal "ro$nosis reducin$ /*#ear survival rates !rom0, to +,.0, to +,.

Common e5trahe"atic sites o! metastaticCommon e5trahe"atic sites o! metastaticdisease include lun$ bone CS and adrenal $lands.disease include lun$ bone CS and adrenal $lands.

8actors that increase the li2elihood o! recurrence8actors that increase the li2elihood o! recurrenceinclude the "resence o! 9include the "resence o! 9 multi"le !oci o! he"atocellular carcinomamulti"le !oci o! he"atocellular carcinoma liver ca"sule invasionliver ca"sule invasion tumor si3e 6</ cm.tumor si3e 6</ cm. Kascular invasion both microsco"ic and macrosco"ic. Kascular invasion both microsco"ic and macrosco"ic.

El*Sera$ %B Tran T Everhart >E. 1iabetes increases the ris2 o! chronic liverEl*Sera$ %B Tran T Everhart >E. 1iabetes increases the ris2 o! chronic liverdisease and he"atocellular carcinoma. )astroenterolo$#. 8eb ;,,-N:;6;9-,*.disease and he"atocellular carcinoma. )astroenterolo$#. 8eb ;,,-N:;6;9-,*.

I l CT t : thIn $eneral a CT scan at : month

In $eneral a CT scan at : monthIn $eneral a CT scan at : month"ostresection."ostresection.

Serum al"ha*!eto"roteinSerum al"ha*!eto"rotein

measurements and re"eat ima$in$measurements and re"eat ima$in$studies 6e$ ultrasound CT MRIstudies 6e$ ultrasound CT MRIever# +* months.ever# +* months.

A!ter ;*+ #ears sa!e to increase the A!ter ;*+ #ears sa!e to increase the!ollow*u" interval.!ollow*u" interval.

Su''ar+ Su''ar+

Earl#*sta$e he"atocellular carcinoma is t#"icall# clinicall# silentEarl#*sta$e he"atocellular carcinoma is t#"icall# clinicall# silent

and %CC is o!ten advanced at 4rst mani!estation.and %CC is o!ten advanced at 4rst mani!estation.

@ithout treatment the /*#ear survival rate is less than /.@ithout treatment the /*#ear survival rate is less than /.

Com"lete sur$ical resection !ollowed b# he"atic trans"lantationCom"lete sur$ical resection !ollowed b# he"atic trans"lantation

oers the best lon$*term survival but !ew "atients are eli$ible !oroers the best lon$*term survival but !ew "atients are eli$ible !or

this thera"#.this thera"#.

Radio!reQuenc# ablation is the "re!erred method !or mana$in$Radio!reQuenc# ablation is the "re!erred method !or mana$in$

unresectable small %CCs that are !ew in number. More wides"readunresectable small %CCs that are !ew in number. More wides"read

disease is treated with "ercutaneous thera"ies such asdisease is treated with "ercutaneous thera"ies such aschemoemboli3ation.chemoemboli3ation.

S#stemic administration o! biolo$ic and chemothera"eutic a$ents isS#stemic administration o! biolo$ic and chemothera"eutic a$ents is

minimall# success!ul in slowin$ the $rowth o! %CC and t#"icall# isminimall# success!ul in slowin$ the $rowth o! %CC and t#"icall# is

used to control s#m"toms in "atients with overwhelmin$ disease.used to control s#m"toms in "atients with overwhelmin$ disease.

A multidisci"linar# a""roach that includes A multidisci"linar# a""roach that includes sur$er# s#stemicsur$er# s#stemic

thera"# and radiation thera"#thera"# and radiation thera"# and that is based on the coo"erationand that is based on the coo"erationo! radiation oncolo$ists interventional and dia$nostic radiolo$istso! radiation oncolo$ists interventional and dia$nostic radiolo$ists

he"atolo$ists and "atholo$ists oer the best chance o! a cure or athe"atolo$ists and "atholo$ists oer the best chance o! a cure or at

least a lon$er and more normal li!e.least a lon$er and more normal li!e.

Liver Tu'orsLiver Tu'ors

A#man Abdo A#man AbdoM1 AmBIM 8RC7CM1 AmBIM 8RC7C

O"3ectiveO"3ective

:.:. Identi!# the most im"ortantIdenti!# the most im"ortant

!eatures o! common beni$n liver!eatures o! common beni$n liver

tumorstumors

;.;. Pnow the ris2 !actors dia$nosisPnow the ris2 !actors dia$nosis

and mana$ement o! he"atocellularand mana$ement o! he"atocellular

carcinomacarcinoma

C!assicationC!assication

5enin M$-in$nt

%eman$ioma%eman$ioma

8ocal nodular8ocal nodular

h#"er"lasiah#"er"lasia Adenoma Adenoma

Liver c#stsLiver c#sts

:.:. 7rimar# liver7rimar# liver

cancerscancers %e"atocellular%e"atocellular

carcinomacarcinoma

8ibrolamellar8ibrolamellar

carcinomacarcinoma

%e"atoblastoma%e"atoblastoma

;. Metastases;. Metastases

%eni(n Liver%eni(n LiverLesionsLesions

:.:. %eman$ioma%eman$ioma

8 l d l h l i8ocal nod lar h "er"lasia

;.;. 8ocal nodular h#"er"lasia8ocal nodular h#"er"lasia

+.+. Adenoma Adenoma

-.-. C#stsC#sts

$e'an(io'a$e'an(io'aC!inica! 0eaturesC!inica! 0eatures

The commonest liver tumorThe commonest liver tumor

/ ! t i/ o! auto"sies

/ o! auto"sies/ o! auto"sies

?suall# sin$le small?suall# sin$le small

@ell demarcated ca"sule@ell demarcated ca"sule ?suall# as#m"tomatic?suall# as#m"tomatic

$e'an(io'a$e'an(io'aDia(nosis and Mana(e'entDia(nosis and Mana(e'ent

1ia$nosis1i

a$nosis ?S9 echo$enic s"ot well demarcated?S9 echo$enic s"ot well demarcated

?S9 echo$enic s"ot well demarcated?S9 echo$enic s"ot well demarcated CT9 venous enhancement !rom "eri"her#CT9 venous enhancement !rom "eri"her#

to centerto center

MRI9 hi$h intensit# areaMRI9 hi$h intensit# area o need !or 8A o need !or 8A

TreatmentTreatment o need !or treatmento need !or treatment

CT)$e'an(io'aCT)$e'an(io'a

0oca! Nodu!ar $+*er*!asia0oca! Nodu!ar $+*er*!asia

0N$K0N$K

C!inica! 0eaturesC!inica! 0eatures Beni$n nodule !ormation o! normalBeni$n nodule !ormation o! normal

liver tissueliver tissue

Central stellate scarCentral stellate scar

More common in #oun$ and middleMore common in #oun$ and middlea$e womena$e women

o relation with se5 hormoneso relation with se5 hormones

?suall# as#m"tomatic?suall# as#m"tomatic Ma# cause minimal "ainMa# cause minimal "ain

0oca! Nodu!ar $+*er*!asia0oca! Nodu!ar $+*er*!asia

0N$K0N$K

Dia(nosis and Mana(e'entDia(nosis and Mana(e'ent1ia$nosis1i

a$nosis99 ?S9 odule with var#in$ echo$enicit#?S9 odule with var#in$ echo$enicit#

# $ $ ## $ $ # CT9 %#"ervascular mass with central scarCT9 %#"ervascular mass with central scar MRI9 iso or h#"o intenseMRI9 iso or h#"o intense

8A9 ormal he"atoc#tes and Pu"er8A9 ormal he"atoc#tes and Pu"ercells with central core.cells with central core.

TreatmentTreatment99

o treatment necessar#o treatment necessar# 7re$nanc# and hormones 'P 7re$nanc# and hormones 'P

CT)0N$CT)0N$

$e*atic Adeno'a$e*atic Adeno'aC!inica! featuresC!inica! features

Beni$n neo"lasm com"osed o! normalBeni$n neo"lasm com"osed o! normalhe"atoc#tes no "ortal tract centralhe"atoc#tes no "ortal tract central

" # " " # " veins or bile ducts veins or bile ducts

More common in womenMore common in women

Associated with contrace"tive hormones Associated with contrace"tive hormones ?suall# as#m"tomatic but ma# have?suall# as#m"tomatic but ma# have

R? "ainR? "ain Mat "resents with ru"ture hemorrha$eMat "resents with ru"ture hemorrha$e

or mali$nant trans!ormation 6ver# rareor mali$nant trans!ormation 6ver# rare

$e*atic Adeno'a$e*atic Adeno'aDia(nosis and Mana(e'entDia(nosis and Mana(e'ent1H1H ?S9 4llin$ de!ect?S9 4llin$ de!ect

$$ CT9 1iuse arterial enhancementCT9 1iuse arterial enhancement MRI9 h#"o or h#"er intense lesionMRI9 h#"o or h#"er intense lesion

8A 9 ma# be needed8A 9 ma# be needed

T5T5 Sto" hormonesSto" hormones

'bserve ever# m !or ; #'bserve ever# m !or ; # I! no re$ression then sur$ical e5cisionI! no re$ression then sur$ical e5cision

Adeno'a Adeno'a

Liver C+stsLiver C+sts

Ma# be sin$le or multi"leMa# be sin$le or multi"le

Ma# be "art o! "ol#c#stic 2idne#Ma# be "art o! "ol#c#stic 2idne#

diseasedisease

7atients o!ten as#m"tomatic7atients o!ten as#m"tomatic o s"eci4c mana$ement reQuiredo s"eci4c mana$ement reQuired

%#dated c#st%#dated c#st

Ma!i(nant LiverMa!i(nant Liver

Ma!i(nant LiverMa!i(nant LiverLesionsLesions

Ma!i(nant Liver Tu'orsMa!i(nant Liver Tu'ors

:.:. %e"atocellular carcinoma 6%CC%e"atocellular carcinoma 6%CC

;; 8ibro lamellar carcinoma o! the8ibro*lamellar carcinoma o! the

;.;. 8ibro*lamellar carcinoma o! the8ibro*lamellar carcinoma o! the

liverliver

%e"atoblastoma%e"atoblastoma-.-. Intrahe"atic cholan$iocarcinomaIntrahe"atic cholan$iocarcinoma

/./. 'thers'thers

$CC2 Incidence$CC2 Incidence

The most common "rimar# liverThe most common "rimar# liver

cancercancer

cancerca ce

The most common tumor in SaudiThe most common tumor in Saudi

menmen

Increasin$ in ?S and all the worldIncreasin$ in ?S and all the world

$CC2 Ris/ 0actors$CC2 Ris/ 0actors

The most im"ortant ris2 !actor isThe most im"ortant ris2 !actor is

cirr&osiscirr&osis !rom an# cause9!rom an# cause9

cirr&osis !rom an# cause9#

:.:. %e"atitis B 6inte$rates in 1A%e"atitis B 6inte$rates in 1A

%e"atitis C%e"atitis C+.+. Alcohol Alcohol

-.-. A(ato5in A(ato5in

/./. 'ther'ther

$CC2 C!inica!$CC2 C!inica!0eatures0eatures

@t loss and R? "ain 6most common@t loss and R? "ain 6most common As#m"tomatic As#m"tomatic

# "# " @orsenin$ o! "re*e5istin$ chronic liver@orsenin$ o! "re*e5istin$ chronic liver

disdis

Acute liver !ailure Acute liver !ailure'=E9'=E9 Si$ns o! cirrhosisSi$ns o! cirrhosis

%ard enlar$ed R? mass%ard enlar$ed R? mass Liver bruit 6rareLiver bruit 6rare

$CC2 Metastases$CC2 Metastases

Rest o! the liverRest o! the liver

7ortal vein7ortal vein

L#m"h nodesL#m"h nodes

Lun$Lun$ BoneBone

BrainBrain

$CC2 S+ste'ic$CC2 S+ste'ic0eatures0eatures

%#"ercalcemia%#"ercalcemia

%#"o$l#cemia%#"o$l#cemia

%#"erli"idemia%#"erli"idemia

%#"erth#roidism%#"erth#roidism

$CC2 !a"s$CC2 !a"s

Labs o! liver cirrhosisLabs o! liver cirrhosis

A87 6Al!a !eto "rotein A87 6Al!a !eto "rotein

Is an %CC tumor mar2erIs an %CC tumor mar2er Kalues more than :,,n$=ml are Kalues more than :,,n$=ml are

hi$hl# su$$estive o! %CChi$hl# su$$estive o! %CC

Elevation seen in more than 0, o!Elevation seen in more than 0, o!"t"t

$CC2 Dia(nosis$CC2 Dia(nosis

Clinical "resentationClinical "resentation

Elevated A87Elevated A87

Tri"hasic CT scan9 ver# earl#Tri"hasic CT scan9 ver# earl#arterial "er!usionarterial "er!usion

MRIMRI

Bio"s#Bio"s#

US2 $CCUS2 $CC

CT2 8enous P&aseCT2 8enous P&ase

CT2 Arteria! P&aseCT2 Arteria! P&ase

$CC2 Pro(nosis$CC2 Pro(nosis Tumor si3eTumor si3e

E5trahe"atic s"readE5trahe"atic s"read

?nderl#in$ liver disease?nderl#in$ liver disease

7t "er!ormance status7t "er!ormance status

$CC2 Liver$CC2 LiverTrans*!antationTrans*!antation

Best available treatmentBest available treatment

Removes tumor and liverRemoves tumor and liver

'nl# i! sin$le tumor less than /cm or'nl# i! sin$le tumor less than /cm or

less than + tumors less than + cmless than + tumors less than + cmeacheach

Recurrence rate is lowRecurrence rate is low

ot widel# availableot widel# available

$CC2 Resection$CC2 Resection 8easible !or small tumors with8easible !or small tumors with

"reserved liver !unction 6no &aundice"reserved liver !unction 6no &aundice

&or "ortal %Tor "ortal %T

Recurrence rate is hi$hRecurrence rate is hi$h

$CC2 Loca! A"!ation$CC2 Loca! A"!ation 8or non resectable "t8or non resectable "t

8or "t with advanced liver cirrhosis8or "t with advanced liver cirrhosis

8or "t with advanced liver cirrhosis"

Alcohol in&ection Alcohol in&ection

Radio!reQuenc# ablationRadio!reQuenc# ablation Tem"orar# measure onl#Tem"orar# measure onl#

Radio 0reQuenc+Radio 0reQuenc+ A"!ation A"!ation

Et&ano! In3ectionEt&ano! In3ection

$CC2$CC2C&e'oe'"o!i5ationC&e'oe'"o!i5ation

In&ect chemothera"# selectivel# inIn&ect chemothera"# selectivel# in

he"atic arter#he"atic arter#

Then in&ect an embolic a$entThen in&ect an embolic a$ent

'nl# in "t with earl# cirrhosis'nl# in "t with earl# cirrhosis

o role !or s#stemic chemothera"#o role !or s#stemic chemothera"#

C&e'oe'"o!i5ationC&e'oe'"o!i5ation

0i"roLa'e!!ar0i"roLa'e!!arCarcino'aCarcino'a

7resents in #oun$ "t 6/*+/7resents in #oun$ "t 6/*+/

ot related to cirrhosisot related to cirrhosis

A87 is normal A87 is normal

CT shows t#"ical stellate scar withCT shows t#"ical stellate scar withradial se"ta showin$ "ersistantradial se"ta showin$ "ersistant

enhancementenhancement

Secondar+ LiverSecondar+ LiverMetastasesMetastases

The most common site !or blood bornThe most common site !or blood bornmetastasesmetastases

etastases Common "rimaries 9 colon breast lun$Common "rimaries 9 colon breast lun$

stomach "ancreases and melanomastomach "ancreases and melanoma

Mild cholestatic "icture 6AL7 L1% withMild cholestatic "icture 6AL7 L1% with"reserved liver !unction"reserved liver !unction

15 ima$in$ or 8A 15 ima$in$ or 8A

Treatment de"ends on the "rimar# cancerTreatment de"ends on the "rimar# cancer

In some cases resection orIn some cases resection orchemoemboli3ation is "ossiblechemoemboli3ation is "ossible

Su''ar+ Su''ar+

5enin M$-in$nt

%eman$ioma%eman$ioma

8ocal nodular8ocal nodular

h#"er"lasiah#"er"lasia Adenoma Adenoma

Liver c#stsLiver c#sts

:.:. 7rimar# liver7rimar# liver

cancerscancers

%e"atocellular%e"atocellularcarcinomacarcinoma

8ibrolamellar8ibrolamellar

carcinomacarcinoma

%e"atoblastoma%e"atoblastoma

;. Metastases;. Metastases

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