acute and chronic liver disease /ccm board review
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Acute&and&Chronic&Liver&Failure&
Jesse&Hall&MD&
&
Professor&of&Medicine,&Anesthesia&&&Cri<cal&Care&
&
Sec<on&Chief,&Pulmonary&and&Cri<cal&Care&
Medicine&
University&of&Chicago&
Faculty&Disclosures&
Dr.$Hall$• $ receives$honoraria$from$the$ACCP$for$this$course$$$$$$$$$$
$and$SEEK$• $ receives$honoraria$from$the$ATS$for$SOTA$• $ receives$honoraria$from$McGraw@Hill$and$Taylor@ $
$ $Francis$publishing$
Learning&Objec<ves&• Acute&liver&failure&
– Define&e<ologies&of&FHF&– Differen<ate&between&encephalopathy&and&cerebral&edema&
– Conduct&a&preItransplanta<on&evalua<on&– Describe&transplant&complica<ons&in&the&ICU&
• Chronic&liver&failure&– Define&pathophysiology&of&portal&hypertension&– Adhere&to&general&suppor<ve&measures&– Describe&complica<ons&of&cirrhosis&
• SBP&and&secondary&peritoni<s&• Hepa<c&encephalopathy&• Hepatorenal&syndrome&• Variceal&hemorrhage&
Acute&Liver&Failure!
Defini<ons!• Acute&Hepa<<s:&&&&
– Acute&liver&parenchymal&injury&from&exposure&to&hepatotoxins&or&infec<ous&agents,&such&as&viral&hepa<<s,&toxins,&alcohol,&or&medica<ons.&
&
• Acute&Liver&Failure:&&&&
– Development&of&liver&dysfunc<on&in&the&sePng&of&severe´&hepa<<s.&&&&
– Features:&&&• Jaundice&&• Coagulopathy&• Encephalopathy&
• Timing:&
– Fulminant&(Trey&and&Davidson,&1970):&within&8&weeks&of&the&onset&of&jaundice&
• hyperacute:&&jaundice&to&encephalopathy&in&0&I&7&d&• ´&7&I&28&d&&• &subacute&(5&I&26&weeks).&
QuesGon$1:$Which$of$the$following$is$the$most$common$cause$of$acute$liver$failure?$
A. Wilson�s$disease$B. HepaGGs$B$C. HepaGGs$C$D. Acetaminophen$overdose$E. Autoimmune$hepaGGs$
E<ology&of&ALF&
NIH$Study$Group;$Hepatology,$April$2008$
Acetaminophen&Toxicity&
• Most&common&cause&of´&liver&failure&
• Low&therapeu<c&index&
– As&li^le&as&5&grams&can&be&toxic&
– Body&size&is&important&
• Treatment&
– Ac<vated&charcoal&if&<&4&hours&since&<me&of&inges<on&
– Acetylcysteine&(PO&or&IV)&• If&above&the&line&on&the&RumackIMa^hew&nomogram&line&
• If&unknown&<me&of&inges<on&and&level&>&10mcg/ml&
• If&>&7.5&gm&inges<on&and&level¬&available&for&>&8&hours&
– Suppor<ve&care&– Intuba<on&with&stage&III&or&IV&encephalopathy&to&prevent&pneumonia&
– ICP&monitoring&if&intubated&and&awai<ng&transplant&
– Liver&transplant&
NAC:&PO&or&IV?&
• No&convincing&evidence&of&improved&outcome&with&IV&prepara<on&
• Anaphylactoid&reac<ons&likely&more&common&with&IV&administra<on&(reported&incidence&with&IV&drug&5&to&15%,&predominance&of&skin&reac<ons)&
• Deaths&have&been&reported&from&these&reac<ons&
• Accordingly,&PO&route&preferred,&IV&used&only&when&gut&administra<on&is&precluded&
Selec<ng&Pa<ents&for&Transplanta<on&
• Major&challenge&in&ALF&is&to&determine&those&who&
will&recover&with&medical&treatment,&those&for&whom&
surgery&is&fu<le,&and&those&in&whom&the&risks&of&
surgery&and&lifelong&immunosuppression&are&jus<fied&
• Perform&the&above&with&the&best&alloca<on&of&organ&
to&pa<ent&(in&the&US,&17&K&pts&on&wai<ng&list,&5&K&
xplants/yr)&
QuesGon$2:$Which$of$the$following$set$of$parameters$is$used$to$calculate$the$MELD$score?$
A. Lactate,$bilirubin,$and$albumin$B. Lactate,$creaGnine,$bilirubin$C. Platelet$count,$INR,$FVII$D. CreaGnine,$bilirubin,$INR$E. Bilirubin,$level$of$encephalopathy,$INR$$
Model&for&Endstage&Liver&Disease&
• MELD&Score&=&10&(.957&*&Cr&+&1.12&*&Tbili&+&1.12&(INR&
+&.643))&
• What&you&should&know&
– Cr,&Bili,&INR&– Designed&to&allow&UNOS&to&be&more&efficient&and&did&so&
– Based&predominantly&on&CLD&but&now&more&widely&applied&
ICU&Management&of&ALF&
• Prophylaxis&against&UGI&Bleed:&&&Acid&suppression&with&H2&blocker,&protonI
pump&inhibitor&or&mucosal&protec<on&with&sucralfate.&
• Coagulopathy:&&&Prophylac<c&use&of&coagula<on&factors&to&prevent&bleeding&
events&is&ineffec<ve&and&discouraged.&&Their&use&can&obscure&early&signs&
(improving&PT)&of&hepa<c&recovery.&
• Sepsis:&&&Sepsis&is&one&of&the&leading&causes&of&death&in&these&pa<ents.&&
Febrile&pa<ents&should&be&panIcultured&and&an<bio<c&therapy&ins<tuted&
early.&
• Hypoglycemia:&&&Severe&liver&injury&markedly&disrupts&glucose&homeostasis&
as&the&liver&is&one&of&the&main&stores&of&glycogen.&&Intravenous&glucose&
infusions&are&a&mainstay&of&treatment.&
• Encephalopathy:&&The&cause&of&encephalopathy&in&the&sePng&of´&liver&
failure&is&cerebral&edema.&&Any&pa<ent&with&grade&II&or&higher&
encephalopathy&should&be&evaluated&for&cerebral&edema&(imaging&studies&of&
the&brain&and/or&intracranial&pressure&monitoring)&
Mechanisms&of&Encephalopathy&
• Chronic&Liver&Disease&– Ammonia,&GABA,&Glutamate&–&Glutamine,&Benzodiazepine&Receptors&
– Treatment&with&lactulose,&neomycin,&lowIprotein&diet&
• Acute&Liver&Failure&&– Cerebral&Edema&&(possible&role&for&NH3)&
– Treatment&with&ICP&monitor,&mannitol,&dialysis,&HOB&eleva<on,&pressure&
control,&induced&coma.&
• Development&of&Grade&III&encephalopathy&is&an&ominous&sign,&
predic<ve&of&poor&outcome&
Grades&of&Encephalopathy&
• Grade&0: &No&altera<on&of&mental&status&
• Grade&I: &Awake&and&responsive&
& & & &Mild&confusion&and&disorienta<on&
& & & &Altered&personality&
& & & &Asterixis&may&or&may¬&be&present&
&
• Grade&II: &Awake,&but&agitated&
& & & &Increasingly&confused&and&disoriented&
& & & &Hallucina<ons&
&
• Grade&III: &Increasing&suppression&of&mental&status&
& & & &Stuporous&but&arousable&to&vocal&or&tac<le&s<muli&
& & & &May&require&endotracheal&tube&for&airway&protec<on&
&
• Grade&IV: &Unresponsive&to&vocal&or&tac<le&s<mula<on&
& & & &Essen<ally&comatose&but&with&intact&pupillary&reflexes&
& & & &Usually&s<ll&withdraw&to&painful&s<muli&
QuesGon$3:$$What$is$true$about$intracranial$pressure$and$ICP$monitors$in$fulminant$hepaGc$failure?$
A. Parenchymal$intracranial$pressure$transducers$are$$preferred$over$subdural$or$epidural$monitors$
B. ICP$monitors$should$be$placed$regardless$of$ability$to$$correct$coagulopathy$$
C. The$increase$in$ICP$is$reversible$by$treatment$with$$lactulose$
D. Cerebral$perfusion$pressure$(MAP$–$ICP)$<$40$mmHg$for$$more$than$4$hours$results$in$irreversible$brain$injury$
E. The$ICP$should$be$measured$twice$daily$
ICP&Monitoring&
• Place&the&Intracranial&Pressure&(ICP)&Monitor&in&the&Epidural&Space&
• ICP&Monitoring&
– Should&be&strongly&considered&when&pa<ents&evolve&from&stage&II&(agitated&confusion)&to&stage&III&(stuporous)&encephalopathy.&
– Maintain&adequate&platelet&count&(>&60,000)&with&platelet&transfusions&and&INR&<&1.5&with&fresh&frozen&plasma,&if&necessary.&
• Treatment&Guidelines&
– Mannitol&is&used&to&control&ICP&in&pa<ents&with&intact&renal&func<on&or&in&those&on&dialysis.&
– Mannitol&is&given&in&0.5&to&1.0&g/kg&doses.&&Serum&electrolytes,&glucose,&and&osmolarity&should&be&checked&every&4&to&6&hours.&&If&ICP&elevated,&osmolarity&<&310,&and&Na&<145,&then&give&mannitol.&&Mannitol&should&be&held&if&the&pa<ent&has&excessive&serum&osmolarity&or&significant&hypernatremia.&
Hall,$Schmidt$&$Wood$Principles$of$CriGcal$Care,$2005$
Acute&alcoholic&hepa<<s&
• May$not$exhibit$all$the$features$of$ALF$• Rapid$onset$of$jaundice,$fever,$ascites,$and$proximal$muscle$loss$
• Liver$typically$large$and$tender$• Aspartate$aminotransferases$levels$>$2x$normal$but$rarely$above$300$IU/ml,$and$AST/ALT$typically$>$2$
NEJM$2009$
NEJM$2011$
174$pts$randomized$Prednisolone$x$4$weeks$NAC$x$5$days$or$not$$Primary$endpt$6$mos$survival$not$diff$Short$term$mortality$improved$$Less$hepatorenal$syndrome$and$$$$$$infecGon$in$NAC$group$
NEJM$2011$
Relapse$to$drinking$in$3$pts$over$two$year$period$
Causes&of&hyperammonemia&in&the&
absence&of&hepatocellular&injury&
Clay$and$Hailine;$Chest$2007$132:1368$
Causes&of&hyperammonemia&in&the&
absence&of&hepatocellular&injury&
Clay$and$Hailine;$Chest$2007$132:1368$
Causes&of&hyperammonemia&in&the&
absence&of&hepatocellular&injury&
Liver&Transplanta<on!
Criteria&for&Liver&Transplanta<on&
in&FHF:&&King�s&College&UK&
Criteria&for&Liver&Transplanta<on&
in&FHF:&&King�s&College&UK&
MELD&Score&for&predic<ng&need&for&liver&
transplant&
Liver&Transplanta<on&in&FHF!
551 Cases Referred
129 Met Tx Criteria 422 Did Not Meet Criteria
39 Tx 90 No Tx
72% 11% 93% Survival
Williams'R,'ILTS'Barcelona'Mee5ng,'June'2003'
Survival&of&ALF&vs&CLD&aser&transplant&
NIH$Study$Group;$Hepatology,$April$2008$
Complica<ons&of&Transplanta<on&
&
&Are&closely&related&to:&
I&PreImorbid&disease&and&condi<on&
I&Transplant&&procedure&
I&Rejec<on&of&the&gras&or&host&
I&Consequences&of&&immunosupression&
May$be$divided$into:$@$NoninfecGous$complicaGons$@$InfecGous$complicaGons$
&
Early&nonIinfec<ous&complica<ons&
• Hemorrhage$• Primary$grak$failure@$1$to$5%$(change$with$DCD?)$• HepaGc$artery$thrombosis$
• Massive$liver$necrosis$• Bile$leak$• HepaGc$abscesses$• U/S$dx$
• Bile$leaks$or$strictures$• Acute$rejecGon$
• 4$@14$days$post$transplant$• Fever,$mild$elevaGon$transaminases$
Chronic&Liver&Failure&(Management&of&
the&Pa<ent&with&Cirrhosis)!
Management&of&the&Pa<ent&with&Cirrhosis!
• Stable&(unlisted)&pa<ent&with&major&new&problem&
(variceal&hemorrhage,&SBP&and&sepsis)&
• Listed&pa<ent&with&deteriora<on&• In&either&case,&cri<cal&care&at&nexus&of&hepatology,&IR,&transplant&surgery,&GI&endoscopy,&etc&
Pathophysiology&of&Portal&Hypertension!
• Normally&2/3&of&hepa<c&flow&is&portal&at&low&
resistance&(portocaval&gradient&2I6&mm&Hg)&
• With&fibrosis,&bridging,&gradient&rises,&portal&flow&
reduced&with&collateral&circula<on&
• Massive&splenic&dila<on,&sequestra<on&
• Ascites&• Hyperdynamic&systemic&circula<on&
Management&of&the&Pa<ent&with&Cirrhosis!
• High&risk&of&infec<on&– Immune&compromise&
– Wider&range&of&organisms&and&prior&healthcare&contact&
– Adjusted&RR&for&hospitaliza<on&related&to&sepsis&2.6&for&cirrhosis,&ARR&for&death&2.0&
– Most&common&site&is&urine,&followed&by&ascites,&blood,&
and&respiratory&tract&
Management&of&the&Pa<ent&with&Cirrhosis!
• Bacterial&peritoni<s&– Any&pa<ent&with&fever&or&abdominal&pain&should&be&
considered&for¶centesis&&
– Dis<nguishing&SBP&from&secondary&peritoni<s&may&be&
difficult&by&exam&
U/S&Guidance&for¶centesis&
U/S&Guidance&for¶centesis&
Management&of&the&Pa<ent&with&Cirrhosis!
SBP& Culture&neg&
neutrocy<c&
ascites&
Bacterascites& Secondary&
peritoni<s&
PMN$Count$(cells/mm3)$
>250$ >250$ <250$ >>250$
Culture$ Single$organism$
NegaGve$ Single$organism$
MulGple$organisms$
Protein$ Usually$low$ Usually$low$ Usually$low$ Usually$>$1g/dl$
LDH$ Normal$ Normal$ Normal$ High$
Glucose$ Normal$ Normal$ Normal$ Low$
Repeat$para$can$be$of$use$to$determine$course$of$ambiguous$findings$
Management&of&SBP/CNNA/BA!
• Most&cases&caused&by&gut&flora&but&Strep&or&
Staph&may&occur&
• Cefotaxime&a&reasonable&empiric&choice&
• If&outpa<ent&quinolone&prophylaxis&is&being&employed,&wider&spectrum&may&be&needed&
• Renal&failure&common&complica<on&(30I40%)&
and&one&study&showed&drama<c&benefit&(ARF&
incidence&and&survival)&from&albumin&1.5&g/kg&at&
dx&and&1&gm/kg&on&d&3&(NEJM&1999;&341:403)&
&
Management&of&the&Pa<ent&with&Cirrhosis!
• HE/PSE&– Precipitants&
• Drugs&• GIH&• Infec<on&• Dehydra<on&• Electrolyte&disturbances&• Hepa<c&decompensa<on&
• Inc&protein&intake&• Uremia&&
• Acidosis&• Portosystemic&shunts&
Management&of&the&Pa<ent&with&Cirrhosis!
• HS/PSE&– A^en<on&to&airway&– Lactulose&
• Standard&rx&• Said&to&dec&transit&<me,&bind&nitrogenous&toxins,&alter&
gut&pH&
– Abx:&metronidazole,&neomycin,&rifaximin&&
– Probio<cs&
Management&of&the&Pa<ent&with&Cirrhosis!
• Hepatorenal&syndrome&
– Implies&exclusion&of&nephrotoxic&drugs,&sepsis,&intrinsic&
renal&disease,&hypovolemia&
– Occurs&in&up&to&39%&of&pts&with&cirrhosis&>&5&years&– Marker&for&poor&outcome&
– Crea<nine&overes<mates&GFR&in&these&pts&
– Should&prompt&considera<on&for&liver&xplant&if&other&
condi<ons&don�t&preclude&this&
Management&of&the&Pa<ent&with&Cirrhosis!
• Hepatorenal&syndrome&
– HRS&Type&IIrapid&progression&of&RF&over&2&weeks&or&less&with&a&2Ifold&increase&in&crea<nine&or&50%&reduc<on&in&
crea<nine&clearance&
– HRS&Type&III&develops&streadily&over&months&with&a&
crea<nine&clearnace&less&than&40&ml/min&
– Median&survival&is&less&than&two&weeks&for&Type&I&and&less&
than&six&months&for&Type&II&
Management&of&the&Pa<ent&with&
Cirrhosis!• Hepatorenal&syndrome&
– Reversing&liver&damage&or&transplant&reverse&the&
condi<on&
– No&role&for&dopamine,&octreo<de&as&single&agents&
– Conflic<ng&data&for&terlipressin&as&single&agent&– Perhaps&benefit&from&combined&therapy&with&
midodrine&and&octreo<de&
• Hepatology&1999;&29:1690&• Dig&Dis&Sci&2007;&52:742&
Management&of&the&Pa<ent&with&
Cirrhosis!• Hepatorenal&syndrome&
– Plasma&expansion&with&albumin&and¶centesis&in&
cri<cally&ill&pts&with&tense&ascites&and&hepatorenal&
syndrome&(Crit&Care&2008&12:1I9&
– 200&ml&20%&albumin&followed&by&large&volume&
paracentesis&
Management&of&the&Pa<ent&with&
Cirrhosis!
Management&of&the&Pa<ent&with&
Cirrhosis!
J Hepatol 2012
SBP&Prophylaxis&for&the&asci<c&cirrho<c&in&
the&ICU&
Mortality&benefit&shown&in&pa<ents&
hospitalized&with&GIH&
May&begin&with&cesriaxone&1&g&IV&daily,&
switch&to&norfloxacin&400&mg&orally&when&
po&begun&
Balloon&Tamponade&
Balloon&Tamponade&
• Pa<ent&will&need&spectacular&access&• Three&devices&
– SengstakenIBlakemore&
– Minnesota&
– LintonINachlas&(large&volume&gastric&balloon&only)&
• Airway,&airway,&airway&• Immobilize,&immobilize,&immobilize&
• Plan&b,&plan&b,&plan&b&
Octreo<de&
• LongIac<ng&analog&of&somatosta<n&
• IV&administra<on&causes&marked&and&rapid&
decrease&in&portal&venous&inflow,&portal&pressure,&
and&intravariceal&pressure&
• While&these&effects&are&transient&bleeding&reduc<on&
and&reduced&risk&of&rebleeding&are&sustained&
Transjugular&Intrahepa<c&
PortalISystemic&Shunt:&
(TIPS)&
• Has&largely&replaced&earlier&surgical&shunts&• Hemostasis&achieved&in&90%&of&pts&
• Complica<ons&
– Misplacement&
– PSE&(30%)&– Hemoly<c&anemia&(10%)&
– TIPS&stenosis&(less&with&coated&devices)&– Vegeta<ve&infec<ons&(rare)&– Acute&cerebral&edema&(very&rare)&
Indica<ons&for&TIPS:&
Nat�l&Dig&Dis&Advisory&Board&
Acute&bleeding¬&successfully&controlled&with&
medical&or&endoscopic&therapy&
Pa<ents&refractory&or&intolerant&to&medical&or&
endoscopic&therapy,&with&recurrent&bleeding&
Bleeding&from&gastric&varices?&
June$2010$
EARLY&USE&OF&TIPS&IN&PATIENTS&
PRESENTING&WITH&VARICEAL&
BLEEDING&
CP$class$C$or$class$B$with$conGnued$bleeding$at$endoscopy$known$to$have$high$failure$rate$63$such$paGents$randomly$assigned$at$24$h$to$either$TIPS$within$72$h$vs$TIPS$s$rescue$therapy$Followed$for$16$mos$for$rebleeding$or$failure$to$control$bleeding$
Management&of&the&Pa<ent&with&Cirrhosis!
One&point& Two&point& Three&point&
Bilirubin$ <2$ 2@3$ >3$
Albumin$ >$3.5$ 3.5@2.8$ <2.8$
INR$ <$1.7$ 1.7@2.3$ >2.3$
Ascites$ Absent$ Mild@Mod$ Severe/refractory$
Encephalopathy$ Absent$ I@II$ III@IV$
Class&A:&5I6&
Class&B:&7I9&
Class&C:&10I15&
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