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Liver FailureLiver Failure

Mackay Memorial Hospital Department of Internal Medicine

Division of GastroenterologyR4 陳泓達

97/6/22

Liver failure:Liver failure:

Clinical syndrome: sudden loss of Clinical syndrome: sudden loss of liver liver

parenchymal and metabolic parenchymal and metabolic functionfunction

Manifest as coagulopathy and Manifest as coagulopathy and

encephalopathyencephalopathy

Acute liver failure :Acute liver failure :

Defined as interval between onset of Defined as interval between onset of the illness and appearance of the illness and appearance of encephalopathy < 8 weeks encephalopathy < 8 weeks

Etiology:Etiology:

Western countries: heterogenous, Western countries: heterogenous, drugs drugs

(acetaminophen, NSAID), viruses(acetaminophen, NSAID), viruses

Developing countries: viruses, Developing countries: viruses, regional regional

Difference (endemic area ?)Difference (endemic area ?)

Journal of Gastroenterology and Hepatology(2002)17,

S268–S273

Acetaminophen toxicityAcetaminophen toxicity Idiosyncratic drug toxicityIdiosyncratic drug toxicity Hepatotropic virusesHepatotropic viruses Miscellaneous causesMiscellaneous causes Indeterminate acute liver failure Indeterminate acute liver failure

(viruses can not be demonstrated ? )(viruses can not be demonstrated ? )

Uncommon causes:Uncommon causes:

Wilson’s disease, other infections Wilson’s disease, other infections (CMV, HSV, (CMV, HSV,

EBV), vascular abnormality, toxin, EBV), vascular abnormality, toxin, acute fatty liver acute fatty liver

of pregnancy, antoimmune hepatitis, of pregnancy, antoimmune hepatitis, ischemia, ischemia,

malignant infiltrationmalignant infiltration

Symptoms and signs:Symptoms and signs:

Jaundice, altered mental status, Jaundice, altered mental status, nausea/ nausea/

vomiting, anorexia, fatigue, malaise,vomiting, anorexia, fatigue, malaise,

myalgia/arthralgiamyalgia/arthralgia

Most of them present Most of them present hepatoencephalopathy hepatoencephalopathy

and icteric appearance. and icteric appearance.

Non-specific Non-specific ManagementManagement

HypoglycemiaHypoglycemiaEncephalopathyEncephalopathyInfectionsInfectionsHemorrhageHemorrhageCoagulopathyCoagulopathyHypotension(hypovolemia, vascular Hypotension(hypovolemia, vascular

resistance ↓)resistance ↓)Respiratory failureRespiratory failureRenal failureRenal failurePancreatitisPancreatitis

Hypoglycemia: monitoring blood Hypoglycemia: monitoring blood glucose, IV glucose supplement.glucose, IV glucose supplement.

Infection: aseptic care, high index of Infection: aseptic care, high index of suspicion, preemptive antibiotic.suspicion, preemptive antibiotic.

Hemorrhage (i.e. GI): NG placement, Hemorrhage (i.e. GI): NG placement, H2 blocker or PPI.H2 blocker or PPI.

Hypotension: hemodynamic Hypotension: hemodynamic monitoring or central pressures, monitoring or central pressures, volume repletion volume repletion

Respiratory failure (ARDS): Respiratory failure (ARDS): mechanical ventilation.mechanical ventilation.

Renal failure (hypovolemia, Renal failure (hypovolemia, hepatorenal syndrome, ATN): hepatorenal syndrome, ATN): hemodynamic monitor, central hemodynamic monitor, central pressure, volume repletion, avoid pressure, volume repletion, avoid nephrotoxic agentnephrotoxic agent

EncephalopathyEncephalopathy

major complication major complication precise mechanism remains unclearprecise mechanism remains unclear Hypothesis: Ammonia productionHypothesis: Ammonia production Treatment toward reducing Treatment toward reducing

ammonia productionammonia production Watch out airway, prevent aspirationWatch out airway, prevent aspiration


Stage 1: day-night reversal, mild Stage 1: day-night reversal, mild confusion, somnolenceconfusion, somnolence

Stage 2: confusion, drowsinessStage 2: confusion, drowsiness Stage 3: stuporStage 3: stupor Stage 4: comaStage 4: coma


Predisposing factorPredisposing factor of hepatic of hepatic encephalopathy:encephalopathy:

GI bleeding, increased protein intake, GI bleeding, increased protein intake, hypokalemic hypokalemic

alkalosis, hyponatremia, infection, alkalosis, hyponatremia, infection, constipation, constipation,

hypoxia, infection, sedatives and hypoxia, infection, sedatives and tranquilizerstranquilizers


TX upon ammonia hypothesisTX upon ammonia hypothesis Correction of hypokalemiaCorrection of hypokalemia Reduction in ammoniagenic Reduction in ammoniagenic

substrates: cleansing enemas and substrates: cleansing enemas and dietary protein restriction.dietary protein restriction.

Lactulose: improved encephalopathy, Lactulose: improved encephalopathy, but not improved outcome. but not improved outcome.

DoseDose 2-3 soft stools per day 2-3 soft stools per day


Oral antibiotics: neomycin Oral antibiotics: neomycin lack of lack of evidenceevidence

nephrotoxicity nephrotoxicity limited use. limited use.

Cerebral EdemaCerebral Edema

Cerebral edema develops in 75 - 80 % Cerebral edema develops in 75 - 80 % of patients with grade IV of patients with grade IV encephalopathy.encephalopathy.

precise mechanism : not completely precise mechanism : not completely understoodunderstood

Possible contributing factor: Possible contributing factor:

osmotic derangement in astrocytesosmotic derangement in astrocytes

changes in cellular metabolismchanges in cellular metabolism

alterations in cerebral blood flow alterations in cerebral blood flow


Clinical manifestations::

↑↑intracranial pressure (ICP) and intracranial pressure (ICP) and brainstem brainstem

Herniation Herniation the most common causes the most common causes of death of death

in fulminant hepatic failurein fulminant hepatic failure

ischemic and hypoxic injury to the brainischemic and hypoxic injury to the brain

hypertension, bradycardia, and irregularhypertension, bradycardia, and irregular

respirations, ↑ muscle tone, hyperreflexia respirations, ↑ muscle tone, hyperreflexia


Monitoring of ICP:Monitoring of ICP:

routinely used by more than one-half routinely used by more than one-half of liver of liver

transplantation programs in the transplantation programs in the United States United States

Tx: to maintain ICP below 20 mmHg Tx: to maintain ICP below 20 mmHg and the CPP above 50 mmHg. and the CPP above 50 mmHg.

CoagulopathyCoagulopathy

diminished capacity of the failing liver diminished capacity of the failing liver to synthesize coagulation factors.to synthesize coagulation factors.

The most common bleeding site: GI The most common bleeding site: GI tract.tract.

Prophylactic administration of FFP: Prophylactic administration of FFP: not recommended.not recommended.

performed before transplant or performed before transplant or invasive procedureinvasive procedure

Specific TreatmentSpecific Treatment

ACT intoxication: charcol followed by NAC

Drug induced hepatotoxicity: discontinue drugs

supportive treatment Viral hepatitis: HBV: anti-HBV treatment, lamivudine HSV/varicella zoster: : acyclovir others: supportive care

Wilson’s disease: early diagnosis Wilson’s disease: early diagnosis liver transplantliver transplant

autoimmune hepatitis: confirm autoimmune hepatitis: confirm diagnosis (liver biopsy), diagnosis (liver biopsy), corticosteroid corticosteroid liver transplantliver transplant

acute fatty liver of pregnancy or the acute fatty liver of pregnancy or the HELLP syndrome: obstetrical HELLP syndrome: obstetrical services, and expeditious delivery services, and expeditious delivery are recommendedare recommended

Acute ischemic injury (shock liver): cardiovascular support

Malignant infiltration: : liver biopsy for diagnosis

treat underlying disease. Indeterminate etiology: consider

biopsy for diagnosis and further guide of treatment

Liver transplantLiver transplant

Liver transplant: remain backbone of Liver transplant: remain backbone of treatment of fulminant hepatic treatment of fulminant hepatic failurefailure

reliable criteria to identify these reliable criteria to identify these patients who really need transplant.patients who really need transplant.

remain unresolved in fulminant remain unresolved in fulminant hepatic failure.hepatic failure.

At King’s College hospital in London (not due to ACT)

either PT>100 second or the presence of any three of the following

variables: 1. age < 10 or > 40 years ;2. an etiology of non-A, non-B hepatitis,

halothane, drug induced liver failure; 3. duration of jaundice before onset of

encephalopathy > 7 days, prothrombin time >50 s, and serum bilirubin > 300 mmol/L.

EncephalopathyEncephalopathy Coagulopathy (PT)Coagulopathy (PT)

Liver transplantLiver transplant Criteria: Criteria: In chronic liver diseaseIn chronic liver diseasemost commonly used prognostic model most commonly used prognostic model MELD score (MELD score (Model for End-stage LiverModel for End-stage LiverDiseaseDisease ) )3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln

INR] INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4+ 9.6[Ln serum creatinine (mg/dL)] + 6.4 Ln: natural logarithm.Ln: natural logarithm.

Liver transplantLiver transplant

CONTRAINDICATIONSCONTRAINDICATIONS: :

1.1. Cardiopulmonary disease can not Cardiopulmonary disease can not be corrected, or preclude surgery.be corrected, or preclude surgery.

2.2. Malignancy outside of the liver Malignancy outside of the liver within 5 years of evaluation, or can within 5 years of evaluation, or can not be cured.not be cured.

3.3. Active alcohol and drug use Active alcohol and drug use

Advanced age and HIV disease: Advanced age and HIV disease: relative contra-indication (site-relative contra-indication (site-specific management)specific management)

Liver support systemLiver support system

Non-cell-based: plasmapheresis and Non-cell-based: plasmapheresis and charcoal-based hemoabsorption charcoal-based hemoabsorption

Cell-based systems : known as Cell-based systems : known as bioartificial liver support systems bioartificial liver support systems

Liver support systemLiver support system

Non-cell-based: not improved survival.

Available systems: molecular adsorbents recirculation

system (MARS) Cell-based systems: undergoing trial.

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