chronic liver disease outline:definitionepidemiology clinical presentation history/pe history/pe...

Chronic Liver Chronic Liver DiseaseDisease

Chronic Liver DiseaseChronic Liver Disease

Outline:Outline:

DefinitionDefinition

EpidemiologyEpidemiology

Clinical PresentationClinical Presentation History/PEHistory/PE LabsLabs RadiographsRadiographs

Management of complicationsManagement of complications Ascites (including HRS, SBP)Ascites (including HRS, SBP) HEHE Variceal hemorrhageVariceal hemorrhage HCCHCC

CLD- PathophysiologyCLD- Pathophysiology When the liver is When the liver is injuredinjured, inflammatory cells infiltrate into the , inflammatory cells infiltrate into the

liver leading to the damage of hepatocytes, which is termed liver leading to the damage of hepatocytes, which is termed ‘‘hepatitis.’’ ‘‘hepatitis.’’

When the injury, regardless of its cause, is prolonged, numerous When the injury, regardless of its cause, is prolonged, numerous mechanisms are initiated to promote healing. mechanisms are initiated to promote healing.

Injured areas become surrounded by scar tissue formed by Injured areas become surrounded by scar tissue formed by excessive deposition of extracellular matrix as a result of excessive deposition of extracellular matrix as a result of activated fibrogenic mechanisms. activated fibrogenic mechanisms.

These processes may lead to These processes may lead to fibrosisfibrosis, which after a period of , which after a period of time leads to irreversible distortion of the hepatic architecture, time leads to irreversible distortion of the hepatic architecture, termed termed ‘‘cirrhosis.’’ ‘‘cirrhosis.’’

Fibrosis develops in almost all patients who have chronic liver Fibrosis develops in almost all patients who have chronic liver injury, albeit at variable rates depending on numerous patient injury, albeit at variable rates depending on numerous patient factors and the underlying liver disease. factors and the underlying liver disease.

Over time, progressive fibrosis ultimately may cause cirrhosis. Over time, progressive fibrosis ultimately may cause cirrhosis.

CLD/Cirrhosis - CLD/Cirrhosis - DefinitionDefinition

The word cirrhosis, derived from the Greek term The word cirrhosis, derived from the Greek term ‘‘kirrhos,’’ refers to a diffuse process in the liver ‘‘kirrhos,’’ refers to a diffuse process in the liver characterized by the development of extensive characterized by the development of extensive fibrosis and replacement of the normal hepatic fibrosis and replacement of the normal hepatic architecture by structurally abnormal nodules of architecture by structurally abnormal nodules of fibrotic tissue. fibrotic tissue.

This structural change in the hepatic architecture This structural change in the hepatic architecture eventually leads to functional changes that are eventually leads to functional changes that are characterized collectively as the syndrome of characterized collectively as the syndrome of chronic liver failure (CLF). chronic liver failure (CLF).

Presence of these changes for more than 6 months Presence of these changes for more than 6 months distinguishes CLF from acute liver failuredistinguishes CLF from acute liver failure


Cirrhosis Cirrhosis

Decompensation HCC Malnutrition Decompensation HCC Malnutrition PulmonaryPulmonary

(HE, ascites, VH) (HE, ascites, VH) Compl.Compl.

(HPS, PPH)(HPS, PPH)

Burden of Liver Disease Burden of Liver Disease in U.S.in U.S.

Prevalence of 5.5 million cases of Prevalence of 5.5 million cases of CLD/cirrhosis in U.S.CLD/cirrhosis in U.S.

Rate of 2030 cases per 100,000 Rate of 2030 cases per 100,000 personspersons

Over 60% of cases are maleOver 60% of cases are male Over 80% are between the ages of 25 Over 80% are between the ages of 25

and 64 yearsand 64 years Little variation in prevalence among Little variation in prevalence among

different racial or ethnic groupsdifferent racial or ethnic groups

Leading Causes of Death Leading Causes of Death in U.S.in U.S.

Chronic liver disease and cirrhosis ranks Chronic liver disease and cirrhosis ranks 1212thth

Age 35-44 years, ranks 7Age 35-44 years, ranks 7thth



Among Hispanics, ranks 7Among Hispanics, ranks 7thth

Among Native Americans, ranks 6Among Native Americans, ranks 6thth

Among Native Americans ages 35-44 years, Among Native Americans ages 35-44 years, cirrhosis is the 2cirrhosis is the 2ndnd leading cause of death leading cause of death

Economic Impact of Economic Impact of Chronic Liver Disease in Chronic Liver Disease in

the U.S.the U.S. $1.5 billion in direct annual costs$1.5 billion in direct annual costs Inpatient staysInpatient stays

$134 million in physician fees$134 million in physician fees $1.1 billion in facility fees$1.1 billion in facility fees

Office visits $64.8 millionOffice visits $64.8 million Medications used to treat Medications used to treat

CLD/cirrhosis $16.9 millionCLD/cirrhosis $16.9 million $234 million in indirect annual costs$234 million in indirect annual costs

Etiology Chronic Liver Etiology Chronic Liver DiseaseDisease

Common:Common: Nonalcoholic Fatty Liver Disease Nonalcoholic Fatty Liver Disease

(NAFLD/NASH)(NAFLD/NASH) Alcoholic liver diseaseAlcoholic liver disease Chronic hepatitis C (CHC)Chronic hepatitis C (CHC) Chronic hepatitis B (CHB)Chronic hepatitis B (CHB)


Less Common:Less Common: Autoimmune hepatitisAutoimmune hepatitis Primary biliary cirrhosis (PBC)Primary biliary cirrhosis (PBC) Primary sclerosing cholangitis (PSC)Primary sclerosing cholangitis (PSC) Drug-induced hepatitisDrug-induced hepatitis GeneticGenetic

Hereditary hemochromatosisHereditary hemochromatosis αα 1 antitrypsin deficiency 1 antitrypsin deficiency TyrosinemiaTyrosinemia Urea cycle disordersUrea cycle disorders Glycogen storage diseasesGlycogen storage diseases


Other/Miscellaneous:Other/Miscellaneous: Secondary biliary cirrhosisSecondary biliary cirrhosis SarcoidosisSarcoidosis Polycystic liver diseasePolycystic liver disease SchistosomiasisSchistosomiasis Idiopathic portal fibrosis (hepatoportal sclerosis)Idiopathic portal fibrosis (hepatoportal sclerosis) Cardiac cirrhosisCardiac cirrhosis Veno-occlusive disease (sinusoidal obstruction Veno-occlusive disease (sinusoidal obstruction

syndrome)syndrome) Budd-Chiari SyndromeBudd-Chiari Syndrome

Etiology of Newly Etiology of Newly Diagnosed CLD in U.S. GI Diagnosed CLD in U.S. GI

PracticesPractices

05

1015202530354045

HCV HCV &ALD

NAFLD ALD HBV Other Insuff.Data

(Am J Gastro 2008)

Deaths due to CLDDeaths due to CLD

Hepatology 2006

HCC:•16,780 deaths in U.S. in 2007

•Third leading cause of death from cancer worldwide

Clinical PresentationClinical Presentation

History:History: Usually asymptomaticUsually asymptomatic Primary focus is on risk factors of Primary focus is on risk factors of

CLDCLD Alcohol historyAlcohol history Jaundiced illnessesJaundiced illnesses IVDU, blood transfusions pre-1991, tattoos, incarcerationsIVDU, blood transfusions pre-1991, tattoos, incarcerations Metabolic syndromeMetabolic syndrome IBDIBD Other autoimmune diseaseOther autoimmune disease Family historyFamily history Medications including OTCs and CAMMedications including OTCs and CAM


Physical Exam:Physical Exam: ““stigmata of chronic liver disease”stigmata of chronic liver disease”

Hepatomegaly/splenomegalyHepatomegaly/splenomegaly Palmar erythemaPalmar erythema Vascular spidersVascular spiders Dupuytren’s contractureDupuytren’s contracture Terry’s nails/leukonychiaTerry’s nails/leukonychia GynecomastiaGynecomastia AsterixisAsterixis AscitesAscites Fetor hepaticusFetor hepaticus


Labs:Labs: ““liver function” is a misnomer liver function” is a misnomer LFT at NMCSD includes: t.bili, d.bili, alt, ast, LFT at NMCSD includes: t.bili, d.bili, alt, ast,

alk phos, ldh, albumin, t.proteinalk phos, ldh, albumin, t.protein Markers of hepatic synthetic function include: Markers of hepatic synthetic function include:

prothrombin time, albumin, bilirubin prothrombin time, albumin, bilirubin Important considerations:Important considerations:

Duration of abnormalityDuration of abnormality Degree of elevation (mild ALT<250, severe Degree of elevation (mild ALT<250, severe

ALT>1000)ALT>1000) Pattern: hepatocellular, cholestatic, mixedPattern: hepatocellular, cholestatic, mixed


Labs:Labs: Hepatocellular pattern:Hepatocellular pattern:

Elevation in ALT and ASTElevation in ALT and AST ALT(xULN)/AP(xULN) ratio = 5 or greaterALT(xULN)/AP(xULN) ratio = 5 or greater

Cholestatic pattern: Cholestatic pattern: Elevation in alkaline phosphate (+/-t.bili)Elevation in alkaline phosphate (+/-t.bili) Other cholestatic enzymes include GGT and Other cholestatic enzymes include GGT and

5’NT5’NT ALT/AP ratio = 2 or lessALT/AP ratio = 2 or less

Mixed pattern:Mixed pattern: Elevation in transaminases and alkaline Elevation in transaminases and alkaline

phosphatasephosphatase ALT/AP ratio = >2 and < 5ALT/AP ratio = >2 and < 5


HepatocellularHepatocellular Viral hepatitisViral hepatitis AIHAIH NAFLDNAFLD ALDALD DILIDILI Hereditary (HH, A1AT, Hereditary (HH, A1AT,

Wilson’s, celiac sprue)Wilson’s, celiac sprue) Ischemic hepatopathyIschemic hepatopathy Congestive hepatopathyCongestive hepatopathy Budd-ChiariBudd-Chiari SOS/VODSOS/VOD CeliacCeliac

CholestaticCholestatic Extrahepatic biliary Extrahepatic biliary

obstructionobstruction PSCPSC PBCPBC DILIDILI SepsisSepsis Post-operative, benignPost-operative, benign Infiltrative (sarcoid, Infiltrative (sarcoid,

lymphoma, tb, amyloid)lymphoma, tb, amyloid)


Labs (specific serologies):Labs (specific serologies):CHC: anti-HCV, HCV RNACHC: anti-HCV, HCV RNACHB: HBsAg, HBV DNACHB: HBsAg, HBV DNAPBC: Antimitochondrial Ab (AMA)PBC: Antimitochondrial Ab (AMA)AIH: ANA, anti smooth muscle Ab (ASMA), AIH: ANA, anti smooth muscle Ab (ASMA),

IgGIgGHH: ferritin, iron saturation, HFE mutationHH: ferritin, iron saturation, HFE mutationWilson’s: ceruloplasmin, 24h urine copperWilson’s: ceruloplasmin, 24h urine copperA1AT deficiency: A1AT level/phenotypeA1AT deficiency: A1AT level/phenotypeCeliac: anti-ttgCeliac: anti-ttg


Labs (nonspecific):Labs (nonspecific): AST:ALT of > 1 (even in setting of normal AST:ALT of > 1 (even in setting of normal

values)values) APRI (AST to platelet ratio index)APRI (AST to platelet ratio index)

(AST/AST ULN)/Plt count x 100(AST/AST ULN)/Plt count x 100 APRI threshold of 0.5 has sens. of 81% and spec of 50% APRI threshold of 0.5 has sens. of 81% and spec of 50%

of predicting advanced fibrosis in patients with CHCof predicting advanced fibrosis in patients with CHC

Low albuminLow albumin Prolonged PT/INRProlonged PT/INR Thrombocytopenia/LeukopeniaThrombocytopenia/Leukopenia MacrocytosisMacrocytosis


Radiographic Studies:Radiographic Studies: UltrasoundUltrasound

First study of choice (inexpensive, easy)First study of choice (inexpensive, easy) CTCT

Liver protocol (triple phase constrast Liver protocol (triple phase constrast study)study)

MRMR With gadolinium enhancementWith gadolinium enhancement Can combine with MRCPCan combine with MRCP


Radiographic Studies (findings):Radiographic Studies (findings): HepatomegalyHepatomegaly Increased echogenicity (hallmark of steatosis)Increased echogenicity (hallmark of steatosis)

Hypodense compared to spleen (steatosis on CT)Hypodense compared to spleen (steatosis on CT) Nodular contour liver edgeNodular contour liver edge Left/Caudate lobe hypertrophyLeft/Caudate lobe hypertrophy

Caudate/Right lobe ratio > 0.65 is 90% specific for Caudate/Right lobe ratio > 0.65 is 90% specific for cirrhosiscirrhosis

SplenomegalySplenomegaly Spleen length > 12cm consistent with Portal HTNSpleen length > 12cm consistent with Portal HTN

Clinical PresenationClinical Presenation

Radiographic Studies (findings):Radiographic Studies (findings): Portal vein diameterPortal vein diameter

>12 mm consistent with Portal HTN>12 mm consistent with Portal HTN AscitesAscites

Can detect as little as 50mlCan detect as little as 50ml Venous collaterallizationVenous collaterallization

Recanalized umbilical vein, varicesRecanalized umbilical vein, varices Portal vein thrombosisPortal vein thrombosis Bowel wall thickeningBowel wall thickening

64% of cirrhotics vs. 7% controls64% of cirrhotics vs. 7% controls HCCHCC

Early aterial enhancing nodules with venous phase Early aterial enhancing nodules with venous phase washoutwashout


Cirrhosis Cirrhosis

Decompensation HCC Malnutrition Decompensation HCC Malnutrition PulmonaryPulmonary

(HE, ascites, VH) (HE, ascites, VH) Compl.Compl.

(HPS, PPH)(HPS, PPH)

Cirrhosis: managementCirrhosis: management(general principles)(general principles)

Addressing underlying diseaseAddressing underlying disease Assessing severityAssessing severity

PrognosisPrognosis Natural historyNatural history

Screening/Surveillance of HCC and Screening/Surveillance of HCC and varicesvarices

Treat decompensation (ascites, HE, Treat decompensation (ascites, HE, etc.)etc.)

PreventivePreventive

Assessing Severity of Assessing Severity of Underlying Liver DiseaseUnderlying Liver Disease

An accurate assessment of extent and An accurate assessment of extent and severity of liver disease is required for severity of liver disease is required for every cirrhoticevery cirrhotic

Two commonly used clinical scoring Two commonly used clinical scoring schemes have both been found to schemes have both been found to correlate with liver-related mortalitycorrelate with liver-related mortality Child-Turcotte-Pugh (CTP)Child-Turcotte-Pugh (CTP) Model for End-Stage Liver Disease Model for End-Stage Liver Disease

(MELD)(MELD)


CTP:CTP: 1964, Child & Turcotte introduced a scoring 1964, Child & Turcotte introduced a scoring

system to predict mortality in patients system to predict mortality in patients undergoing portocaval shunt surgeryundergoing portocaval shunt surgery

5 significant factors that affected mortality5 significant factors that affected mortality1.1. AscitesAscites2.2. AlbuminAlbumin3.3. BilirubinBilirubin4.4. EncephalopathyEncephalopathy5.5. Nutritional statusNutritional status

• • 1972, Pugh substituted the most subjective 1972, Pugh substituted the most subjective factor (nutritional status) with prothrombin factor (nutritional status) with prothrombin timetime

Modified Child-Pugh ScoreModified Child-Pugh Score

PresentationPresentation 11 22 33Albumin Albumin

(g/dl)(g/dl)> 3.5> 3.5 2.8 - 3.52.8 - 3.5 < 2.8< 2.8

Prothrombin Prothrombin time (INR)time (INR)

< 1.7< 1.7 1.7 - 2.31.7 - 2.3 > 2.3> 2.3

Bilirubin Bilirubin (mg/dl)(mg/dl)

< 2< 2 2 - 32 - 3 > 3> 3

AscitesAscites AbsentAbsent Slight - Slight - mod.mod.

TenseTense

EncephalopaEncephalopathythy

NoneNone Gr. I - IIGr. I - II Gr. III - IVGr. III - IV

*Class A = 5-6 points, B = 7-9 points, C = 10-15 points*Class A = 5-6 points, B = 7-9 points, C = 10-15 points

**For cholestatic disorders (eg, PBC) assign 1 point for bilirubin < 4mg/dl, 2 points for 4-10mg/dl, and 3 points for >10mg/dl

Points*


MELD:MELD: Originally devised as a prognostic measure of Originally devised as a prognostic measure of

short term mortality in patients undergoing short term mortality in patients undergoing transjugular intrahepatic portosystemic shunttransjugular intrahepatic portosystemic shunt¹¹

Patients are assigned a score of 6-40Patients are assigned a score of 6-40 The score incorporates 3 biochemical variablesThe score incorporates 3 biochemical variables

1.1. Total bilirubinTotal bilirubin

2.2. Serum creatinineSerum creatinine

3.3. INRINR

(¹Malinchoc, Hepatology 2000)

MELDMELD


MELD:MELD: Prospectively validated as a prognostic Prospectively validated as a prognostic

marker of mortality in cirrhosis, acute marker of mortality in cirrhosis, acute alcoholic hepatitis, acute variceal alcoholic hepatitis, acute variceal bleedingbleeding

Possible use in acetaminophen-induced Possible use in acetaminophen-induced liver injury, HRS, cirrhosis with sepsis, liver injury, HRS, cirrhosis with sepsis, and UNOS Status 1and UNOS Status 1

Feb. 2002 – MELD was adopted by Feb. 2002 – MELD was adopted by UNOS for the purpose of donor liver UNOS for the purpose of donor liver allocationallocation

Cirrhosis: PrognosisCirrhosis: Prognosis

1 year survival:1 year survival: Child’s A: 100% Child’s A: 100% Child’s B: 80% Child’s B: 80% Child’s C: 45% Child’s C: 45%

2 year survival2 year survival Child’s A: 85%Child’s A: 85% Child’s B: 60%Child’s B: 60% Child’s C: 35%Child’s C: 35%


The median survival of patients with The median survival of patients with compensated cirrhosis is 7-10 years compensated cirrhosis is 7-10 years from the time of diagnosisfrom the time of diagnosis

2 year survival after clinical 2 year survival after clinical decompensation is below 50%decompensation is below 50%

Decompensation event rates range Decompensation event rates range between 5 and 10% annuallybetween 5 and 10% annually


Decompensation/Disease-related Decompensation/Disease-related complicationscomplications

8% annual risk of developing esophageal 8% annual risk of developing esophageal varicesvarices

5-15% annual risk of variceal hemorrhage5-15% annual risk of variceal hemorrhage 5-6% annual risk of developing hepatic 5-6% annual risk of developing hepatic

encephalopathy and/or ascitesencephalopathy and/or ascites 1-6% annual risk of developing 1-6% annual risk of developing

hepatocellular carcinomahepatocellular carcinoma

Management of Selected Management of Selected Complications of Cirrhosis: Complications of Cirrhosis:

VaricesVaricesAcute Variceal Hemorrhage:Acute Variceal Hemorrhage: 40% risk reduction in mortality in AVH in 2000 40% risk reduction in mortality in AVH in 2000

compared to historical controls from the 1960s (using compared to historical controls from the 1960s (using endoscopic variceal ligation and pharmacologic endoscopic variceal ligation and pharmacologic therapy)therapy)

Primary prophylaxis:Primary prophylaxis: Nonselective Beta blockers reduce the risk of first Nonselective Beta blockers reduce the risk of first

bleeding from 25% to 15% (RRR 40%, NNT 10)bleeding from 25% to 15% (RRR 40%, NNT 10)

Secondary prophylaxis:Secondary prophylaxis: Combination EVL plus NSBB is better than either Combination EVL plus NSBB is better than either

alonealone Recent randomized trial (combo v EVL) reduced Recent randomized trial (combo v EVL) reduced

rebleeding rate from 38% to 14%rebleeding rate from 38% to 14%


VaricesVarices All cirrhotics eligible for the benefits All cirrhotics eligible for the benefits

of 1° prophylaxis should undergo of 1° prophylaxis should undergo EGD to exclude the presence of EGD to exclude the presence of esophageal varicesesophageal varices

When no or small EV are found in When no or small EV are found in Child A cirrhotics, 1° prophylaxis Child A cirrhotics, 1° prophylaxis not recommended and EGD should not recommended and EGD should be repeated at 2-3 yr intervalsbe repeated at 2-3 yr intervals

EVL may be used as 1° prophylaxis EVL may be used as 1° prophylaxis for those who are intolerant of NSBBfor those who are intolerant of NSBB


VaricesVarices Management of acute variceal Management of acute variceal

hemorrhage should include:hemorrhage should include: EVLEVL Vasoactive drug therapy for at least 5 Vasoactive drug therapy for at least 5

days (Octreotide 50mcg bolus then days (Octreotide 50mcg bolus then 50mcg/h gtt) 50mcg/h gtt)

antibiotic prophylaxis (oral norfloxacin antibiotic prophylaxis (oral norfloxacin 400 mg twice daily for 7 days or 400 mg twice daily for 7 days or intravenous ceftriaxone 1g/d)intravenous ceftriaxone 1g/d)


Ascites and SBPAscites and SBP Primary treatment of patients with Primary treatment of patients with

cirrhosis and ascites is:cirrhosis and ascites is: (1) sodium restriction (1) sodium restriction (2) oral diuretics. (2) oral diuretics.

Sodium restriction (not fluid restriction) Sodium restriction (not fluid restriction) results in weight loss as water follows results in weight loss as water follows sodium passively.sodium passively.

Dietary sodium restriction and diuretic Dietary sodium restriction and diuretic therapy is successful in controlling ascites therapy is successful in controlling ascites in 90% of patients. in 90% of patients.


Ascites and SBPAscites and SBPSodium Restriction:Sodium Restriction: The goal is to restrict intake to less than The goal is to restrict intake to less than

2000mg/day (88 mmol/d). To reduce or 2000mg/day (88 mmol/d). To reduce or stabilize accumulation of ascites, net stabilize accumulation of ascites, net urinary excretion of sodium needs to be at urinary excretion of sodium needs to be at least 78 mmol/d.least 78 mmol/d.

(88mmol – 10mmol (insensible losses)) = 78 (88mmol – 10mmol (insensible losses)) = 78 mmol/d.mmol/d.

A random “spot” urine Na:K > 1 correlates A random “spot” urine Na:K > 1 correlates with a 24 hour Na excretion of > 78 with a 24 hour Na excretion of > 78 mmol/d with approximately 90% accuracymmol/d with approximately 90% accuracy


Ascites and SBPAscites and SBPDiureticsDiuretics Aldosterone AntagonistsAldosterone Antagonists

Increased aldosterone levels contribute to avid retention of Increased aldosterone levels contribute to avid retention of sodium and the development of ascites, drugs that block sodium and the development of ascites, drugs that block aldosterone (spironolactone) are 1st line agents in producing aldosterone (spironolactone) are 1st line agents in producing diuresis in the setting of ascitesdiuresis in the setting of ascites..

Loop diureticsLoop diuretics Loop diuretics inhibit chloride reabsorption in the Loop diuretics inhibit chloride reabsorption in the

ascending limb of the loop of Henle which increases the ascending limb of the loop of Henle which increases the sodium, chloride, and water delivered to the distal tubule. sodium, chloride, and water delivered to the distal tubule. It is this action that limits the use of loop diuretics as It is this action that limits the use of loop diuretics as single agents given that all of the sodium delivered to the single agents given that all of the sodium delivered to the distal tubule will be reabsorbed because of unopposed distal tubule will be reabsorbed because of unopposed action of aldosterone. However when combined with action of aldosterone. However when combined with spironolactone, loop diuretics result in marked natruiresis.spironolactone, loop diuretics result in marked natruiresis.

Typically begin Aldactone 100mg/d with Lasix Typically begin Aldactone 100mg/d with Lasix 40mg/d and titrate up in that ratio40mg/d and titrate up in that ratio


Ascites and SBPAscites and SBP Spontaneous bacterial peritonitis (SBP) Spontaneous bacterial peritonitis (SBP)

is present in 3.5% of hospitalized is present in 3.5% of hospitalized outpatients and increases to 10-30% in outpatients and increases to 10-30% in inpatientsinpatients

Mortality has decreased from 30-50% to Mortality has decreased from 30-50% to 8-17% with advances in diagnosis and 8-17% with advances in diagnosis and treatmenttreatment

All hospitalized patients with ascites All hospitalized patients with ascites (especially those with GI bleed) should (especially those with GI bleed) should undergo diagnostic paracentesisundergo diagnostic paracentesis


Ascites and SBPAscites and SBPSBP Treatment:SBP Treatment: Intial therapy typically includes 3Intial therapy typically includes 3rdrd

generation cephalosporin for 5 daysgeneration cephalosporin for 5 days Cefotaxime has been most extensively studied Cefotaxime has been most extensively studied

(2g IV every 8 hours(2g IV every 8 hours 100% penetration of ascitic fluid and sterilizes 100% penetration of ascitic fluid and sterilizes

the fluid in 94% of cases after single dosethe fluid in 94% of cases after single dose Intravenous albumin at 1.5g/kg on day 1 Intravenous albumin at 1.5g/kg on day 1

and 1g/kg on day 3and 1g/kg on day 3 Has shown to decrease frequency of renal Has shown to decrease frequency of renal

impairment and reduce short and intermediate-impairment and reduce short and intermediate-term mortality in single prospective randomized term mortality in single prospective randomized trialtrial

(Sort, NEJM 1999)(Sort, NEJM 1999)


Ascites and SBPAscites and SBPSBP prophylaxis:SBP prophylaxis:1.1. Any cirrhotic with acute GI bleedAny cirrhotic with acute GI bleed2.2. History of SBPHistory of SBP

Patients with previous episode of SBP Patients with previous episode of SBP have 70% chance of recurrence at 1 yearhave 70% chance of recurrence at 1 year

3.3. Hospitalized cirrhotics with low Hospitalized cirrhotics with low protein (<1g/dl) ascitesprotein (<1g/dl) ascites

Single study of norfloxacin reduced Single study of norfloxacin reduced incidence incidence of SBP from 22.5% to incidence incidence of SBP from 22.5% to 0% 0%

(Soriano, Gastroenterology 1999)(Soriano, Gastroenterology 1999)


Ascites and SBPAscites and SBPSBP prophylaxis:SBP prophylaxis:

4.4. Cirrhotics with low protein ascites Cirrhotics with low protein ascites (<1.5) and advanced liver failure (<1.5) and advanced liver failure (CPT ≥ 9) with bili ≥ 3mg OR Cr ≥ (CPT ≥ 9) with bili ≥ 3mg OR Cr ≥ 1.2, BUN ≥ 25 or Na ≤ 1301.2, BUN ≥ 25 or Na ≤ 130

Single study using daily norfloxacin Single study using daily norfloxacin reduced 1 year probablility of SBP and reduced 1 year probablility of SBP and HRS as well as improved 3 month and 1 HRS as well as improved 3 month and 1 year survivalyear survival

(Fernandez, Gastroenterology 2007)(Fernandez, Gastroenterology 2007)


EncephalopathyEncephalopathyPortosystemic Encephalopathy:Portosystemic Encephalopathy:

Pathogenesis is complex but ammonia is a Pathogenesis is complex but ammonia is a key factorkey factor

The diagnosis is one of exclusionThe diagnosis is one of exclusion Precipitating factors: electrolyte Precipitating factors: electrolyte

disturbances (hypokalemia), alkalosis, disturbances (hypokalemia), alkalosis, hypovolemia, medications (benzos, hypovolemia, medications (benzos, narcotics), infection (UTI, SBP), GI narcotics), infection (UTI, SBP), GI bleeding, constipation, surgerybleeding, constipation, surgery


EncephalopathyEncephalopathyPSE management:PSE management: Fix/remove precipitating factorsFix/remove precipitating factors Nonabsorbable dissacharidesNonabsorbable dissacharides AntibioticsAntibiotics Don’t restrict protein!Don’t restrict protein!

No clinical evidence to support this practice No clinical evidence to support this practice and has potential to complicate postoperative and has potential to complicate postoperative course (often have preexisting malnutrition)course (often have preexisting malnutrition)

Need 1-1.5g/kg/dNeed 1-1.5g/kg/d Miscellaneous: BCAA, probiotics, Miscellaneous: BCAA, probiotics,

flumazenil, Zinc, melatoninflumazenil, Zinc, melatonin


EncephalopathyEncephalopathyPSE management:PSE management: LactuloseLactulose

Paucity of placebo controlled clinical trials but Paucity of placebo controlled clinical trials but extensive clinical experienceextensive clinical experience

Cheap!Cheap! RifaximinRifaximin

Metanalysis showed rifaximin to be as effective Metanalysis showed rifaximin to be as effective and in many studies for effective than and in many studies for effective than nonabsorbable dissacharidesnonabsorbable dissacharides

(Lawrence, Pharmacotherapy 2008)(Lawrence, Pharmacotherapy 2008) Recent study showed fewer hospitalizations, fewer Recent study showed fewer hospitalizations, fewer

days hospitalized, fewer total weeks hospitalized days hospitalized, fewer total weeks hospitalized and lower hospitalization charges per patient and lower hospitalization charges per patient (rifaximin v. lactulose)(rifaximin v. lactulose)

(Leevy, Dig Dis Sci 2007)(Leevy, Dig Dis Sci 2007)

Management of Selected Management of Selected Complications of Cirrhosis: Complications of Cirrhosis: Hepatocellular CarcinomaHepatocellular Carcinoma

HCC screening is recommended in high risk HCC screening is recommended in high risk patientspatients

Recent analysis of HCC screening practices Recent analysis of HCC screening practices across 3 VA centers showedacross 3 VA centers showed 28% received any screening test within 3 years28% received any screening test within 3 years 7% had two sequential tests reflecting actual 7% had two sequential tests reflecting actual

surveillance guidelines surveillance guidelines (Dawla, J Clin Gastroenterol 2007)(Dawla, J Clin Gastroenterol 2007)

Adherence to surveillance strategy has Adherence to surveillance strategy has shown a 37% reduction in HCC-related shown a 37% reduction in HCC-related mortalitymortality

(Zhang, J Cancer Res Clin Oncol 2004)(Zhang, J Cancer Res Clin Oncol 2004)

Management of Selected Management of Selected Complications of Cirrhosis: Complications of Cirrhosis: Hepatocellular CarcinomaHepatocellular Carcinoma

High risk groups requiring High risk groups requiring screening:screening:

CHB (+HBsAg)CHB (+HBsAg) Asian males > 40Asian males > 40 Asian females > 50Asian females > 50 All cirrhoticsAll cirrhotics Family history of HCCFamily history of HCC Africans over age 20Africans over age 20Nonhepatitis B cirrhosisNonhepatitis B cirrhosis Hepatitis CHepatitis C Alcoholic cirrhosisAlcoholic cirrhosis HemochromatosisHemochromatosis PBCPBC Possible (A1AT, NASH, Possible (A1AT, NASH,

AIH)AIH)

AASLD guidelines:AASLD guidelines: AFP + ultrasound AFP + ultrasound

every 6-12 monthsevery 6-12 months

EASL guidelines:EASL guidelines: AFP + ultrasound AFP + ultrasound

every 6 monthsevery 6 months

APASL guidelines:APASL guidelines: HBV patients every 3-HBV patients every 3-

6 months6 months Method not specifiedMethod not specified

chronic liver disease outline:definitionepidemiology clinical presentation history/pe history/pe...

Documents

chronic liver injury

underlying liver disease

pphburden of liver disease

termed cirrhosis

progressive fibrosis

cases of cldcirrhosis

termed hepatitis

normal hepatic architecture