Acute liver failureAcute liver failureTutorialTutorial

Ayman Abdo Ayman Abdo MD, FRCPCMD, FRCPC

ObjectivesObjectives

To identify common causes of acute liver To identify common causes of acute liver failure through history and examinationfailure through history and examination

To recognize common presentationsTo recognize common presentations

To be familiar with medical managementTo be familiar with medical management

To know when to refer a patient for To know when to refer a patient for transplantationtransplantation

Acute Liver FailureAcute Liver FailureDefinitionDefinition

1.1. Rapid hepatocellular Rapid hepatocellular dysfunctiondysfunction

2.2. Encephalopathy Encephalopathy

3.3. No pre-existing liver No pre-existing liver diseasedisease

Common causes of acute liver failureCommon causes of acute liver failure

Viral hepatitis: Hep A, Hep BViral hepatitis: Hep A, Hep B

Toxin/drugToxin/drug

IschemicIschemic

Autoimmune hepatitisAutoimmune hepatitis

Wilson disease Wilson disease

Pt 1: Initial historyPt 1: Initial history

66 y old female66 y old female

Chronic abdominal pain and constipationChronic abdominal pain and constipation

Otherwise healthyOtherwise healthy

3 day history of jaundice and confusion3 day history of jaundice and confusion

Patient 1Patient 1

What other questions What other questions are you going to ask?are you going to ask?

Important questions on historyImportant questions on history

Recent travelRecent travelSexual exposureSexual exposureIVDUIVDUContact with jaundiced ptContact with jaundiced ptDetailed drug history including herbsDetailed drug history including herbsAutoimmune featuresAutoimmune featuresNeurological symptomsNeurological symptomsRecent hypotension or sepsesRecent hypotension or sepses

Pt 1 : More historyPt 1 : More history

Dx to have IBSDx to have IBS

Started on herbal medication 1 week agoStarted on herbal medication 1 week ago

No viral hepatitis risk factorsNo viral hepatitis risk factors

No hypercoagulable disorderNo hypercoagulable disorder

No new medicationsNo new medications

Patient 1Patient 1

What physical signs are What physical signs are you going to look for?you going to look for?

Physical examinationPhysical examination

Vital signsVital signs

Level of concisenessLevel of conciseness

Flapping tremorFlapping tremor

Stigmata of chronic liver diseaseStigmata of chronic liver disease

Ophthalmology exam if indicatedOphthalmology exam if indicated

Full abdominal examinationFull abdominal examination

Full neurological examinationFull neurological examination

Patient 1Patient 1

What labs are you going What labs are you going to order?to order?

Important labsImportant labs

CBC and electrolytesCBC and electrolytesLiver enzymes : ALT, AST, ALP, GGT, LDHLiver enzymes : ALT, AST, ALP, GGT, LDHLiver function tests: INR, Albumine, BiliLiver function tests: INR, Albumine, BiliViral hep serology= HAV IgM, Hep B cAb IgM, Viral hep serology= HAV IgM, Hep B cAb IgM, HCV RNAHCV RNAToxic screen: Acetaminophen levelToxic screen: Acetaminophen levelAIH markers: ANA, ASMAAIH markers: ANA, ASMAWilson: Ceruloplasmin, urine cupperWilson: Ceruloplasmin, urine cupperOthersOthers

Causes of acute liver failureCauses of acute liver failure

Viral hepatitis: Hep A, Hep BViral hepatitis: Hep A, Hep B

Toxin/drugToxin/drug

IschemicIschemic

Autoimmune hepatitisAutoimmune hepatitis

Wilson disease Wilson disease

Lab investigationsLab investigations

CBCCBC

ElectrolytesElectrolytes

Liver enzymes (ALT, AST, ALP, GGT, LDH)Liver enzymes (ALT, AST, ALP, GGT, LDH)

Liver function tests (Bili, Albumin, INR)Liver function tests (Bili, Albumin, INR)

Hep A (IgM, IgG), Hep B (HBsAG, HBcIgM)Hep A (IgM, IgG), Hep B (HBsAG, HBcIgM)

Acetaminophen levelAcetaminophen level

ANAANA

Cerulopasmin, 24 h copper collectionCerulopasmin, 24 h copper collection

Pattern in Ischemic hepatitisPattern in Ischemic hepatitis

Ischemic vs. viralIschemic vs. viral

Get more information ?Get more information ?

ComplicationsComplications&&

ManagementManagement

Specific therapySpecific therapy

Viral:Viral:

Ischemic:Ischemic:

Toxic: Toxic:

Acetaminophen (N-acetyl cystein)Acetaminophen (N-acetyl cystein)

AutoimmuneAutoimmune

WilsonWilson

Which pt will recover with Which pt will recover with intensive medical therapy and intensive medical therapy and

which pt requires which pt requires transplantation?transplantation?

King’s College CriteriaKing’s College Criteria

AcetaminophenAcetaminophen

pH < 7.3pH < 7.3

oror

Grade III or IV HE Grade III or IV HE andand– INR > 6.5INR > 6.5– Creatinine > 300Creatinine > 300

Non-acetaminophenNon-acetaminophenINR > 6.5INR > 6.5or any 3/6or any 3/6– AAge <10 or >40 yrsge <10 or >40 yrs– BBili > 300ili > 300– CCoagulopathy: INR > 3.5oagulopathy: INR > 3.5– DDuration of jaundice uration of jaundice

> 7 days before HE> 7 days before HE– EEtiology: Non A-E, other drugtiology: Non A-E, other drug

O’Grady et al. Gastroenterology 1989;97:439

MARS : Molecular adsorbents recycling system

More quick casesMore quick cases

Case 2Case 2

A 33 y old femaleA 33 y old female

Just came back from UmrahJust came back from Umrah

Has 2 day history of dark urine and yellow Has 2 day history of dark urine and yellow eyeseyes

No new medicationsNo new medications

Patient 2Patient 2

What are the possible What are the possible causes of this causes of this presentation?presentation?

Case 2Case 2

No physical signs except for jaundiceNo physical signs except for jaundice

No encephalopathyNo encephalopathy

ALT=2300, AST=1700, ALP=480, ALT=2300, AST=1700, ALP=480, GGT=789, INR=2.1GGT=789, INR=2.1

Patient 2Patient 2

How would you manage How would you manage this patient?this patient?

Patient 3Patient 3

55 y old male 55 y old male

Massive acute MIMassive acute MI

Successful resuscitationSuccessful resuscitation

Cardiac condition stableCardiac condition stable

5 days later: ALT=2300, AST=2000, 5 days later: ALT=2300, AST=2000, LDH=4500LDH=4500

Patient 3Patient 3

What is the most likely What is the most likely cause?cause?

Patient 3Patient 3

How would you manage How would you manage this patient?this patient?

Patient 4Patient 4

22 y old male22 y old male

Previously healthyPreviously healthy

1 week history of jaundice 1 week history of jaundice

ALT=1500, AST=3400, ALP=450, INR=1.8ALT=1500, AST=3400, ALP=450, INR=1.8

CBC= HB=7.8, WBC=10.8, PLt=340CBC= HB=7.8, WBC=10.8, PLt=340

Patient 4Patient 4

What is the most likely What is the most likely cause?cause?

Patient 4Patient 4

Cerulopasmin= very lowCerulopasmin= very low

24 urinary cupper= very high24 urinary cupper= very high

Ophthalmology exam= KFROphthalmology exam= KFR

ConclusionConclusion

The most important three causes of acute liver The most important three causes of acute liver failure are : viral hepatitis, toxic hepatitis, and failure are : viral hepatitis, toxic hepatitis, and ischemic hepatitisischemic hepatitis

Less likely causes include: Autoimmune Less likely causes include: Autoimmune hepatitis, Wilson disease, malignant infiltrationhepatitis, Wilson disease, malignant infiltration

Early recognition and treatment of the causeEarly recognition and treatment of the cause

Medical management of complicationMedical management of complication

Decide early about transplantationDecide early about transplantation