Liver Failure
Mackay Memorial Hospital
Department of Internal Medicine
Division of Gastroenterology
R4 陳泓達
97/6/22
 Liver
failure:
Clinical syndrome: sudden loss of liver
parenchymal and metabolic function
Manifest as coagulopathy and
encephalopathy
Acute liver failure :
Defined as interval between onset of the illness
and appearance of encephalopathy < 8 weeks

Etiology:
Western countries: heterogenous, drugs
(acetaminophen, NSAID), viruses
Developing countries: viruses, regional
Difference (endemic area ?)

Journal of Gastroenterology and Hepatology(2002)17,
S268–S273
 Acetaminophen
toxicity
 Idiosyncratic drug toxicity
 Hepatotropic viruses
 Miscellaneous causes
 Indeterminate acute liver failure (viruses can not
be demonstrated ? )
Uncommon causes:
Wilson’s disease, other infections (CMV, HSV,
EBV), vascular abnormality, toxin, acute fatty liver
of pregnancy, antoimmune hepatitis, ischemia,
malignant infiltration

Symptoms and signs:
Jaundice, altered mental status, nausea/
vomiting, anorexia, fatigue, malaise,
myalgia/arthralgia
Most of them present hepatoencephalopathy
and icteric appearance.

Non-specific Management
Hypoglycemia
Encephalopathy
Infections
Hemorrhage
Coagulopathy
Hypotension(hypovolemia, vascular resistance ↓)
Respiratory failure
Renal failure
Pancreatitis
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Hypoglycemia: monitoring blood glucose, IV
glucose supplement.
Infection: aseptic care, high index of suspicion,
preemptive antibiotic.
Hemorrhage (i.e. GI): NG placement, H2
blocker or PPI.
Hypotension: hemodynamic monitoring or
central pressures, volume repletion
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Respiratory failure (ARDS): mechanical
ventilation.
Renal failure (hypovolemia, hepatorenal
syndrome, ATN): hemodynamic monitor,
central pressure, volume repletion, avoid
nephrotoxic agent
Encephalopathy
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major complication
precise mechanism remains unclear
Hypothesis: Ammonia production
Treatment toward reducing ammonia production
Watch out airway, prevent aspiration
Encephalopathy
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Stage 1: day-night reversal, mild confusion,
somnolence
Stage 2: confusion, drowsiness
Stage 3: stupor
Stage 4: coma
Encephalopathy
Predisposing factor of hepatic encephalopathy:
GI bleeding, increased protein intake, hypokalemic
alkalosis, hyponatremia, infection, constipation,
hypoxia, infection, sedatives and tranquilizers
Encephalopathy
TX upon ammonia hypothesis
 Correction of hypokalemia
 Reduction in ammoniagenic
substrates: cleansing enemas and dietary protein
restriction.
 Lactulose: improved encephalopathy, but not
improved outcome.
Dose 2-3 soft stools per day
Encephalopathy

Oral antibiotics: neomycin  lack of evidence
nephrotoxicity  limited use.
Cerebral Edema
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Cerebral edema develops in 75 - 80 % of
patients with grade IV encephalopathy.
precise mechanism : not completely understood
Possible contributing factor:
osmotic derangement in astrocytes
changes in cellular metabolism
alterations in cerebral blood flow
Cerebral Edema
Clinical manifestations:
↑intracranial pressure (ICP) and brainstem
Herniation  the most common causes of death
in fulminant hepatic failure
ischemic and hypoxic injury to the brain
hypertension, bradycardia, and irregular
respirations, ↑ muscle tone, hyperreflexia
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Cerebral Edema
Monitoring of ICP:
routinely used by more than one-half of liver
transplantation programs in the United States
 Tx: to maintain ICP below 20 mmHg and the
CPP above 50 mmHg.
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Coagulopathy
diminished capacity of the failing liver to
synthesize coagulation factors.
 The most common bleeding site: GI tract.
 Prophylactic administration of FFP: not
recommended.
 performed before transplant or invasive
procedure
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Specific Treatment
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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
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Wilson’s disease: early diagnosis  liver
transplant
autoimmune hepatitis: confirm diagnosis (liver
biopsy), corticosteroid liver transplant
acute fatty liver of pregnancy or the HELLP
syndrome: obstetrical services, and expeditious
delivery are 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
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Liver transplant
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Liver 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.
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.
 Encephalopathy
 Coagulopathy
(PT)
Liver transplant
Criteria:
In chronic liver disease
most commonly used prognostic model
MELD score (Model for End-stage Liver
Disease )
3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR]
+ 9.6[Ln serum creatinine (mg/dL)] + 6.4
Ln: natural logarithm.
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Liver transplant
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1.
2.
3.
CONTRAINDICATIONS:
Cardiopulmonary disease can not be corrected,
or preclude surgery.
Malignancy outside of the liver within 5 years
of evaluation, or can not be cured.
Active alcohol and drug use
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Advanced age and HIV disease: relative contraindication (site-specific management)
Liver support system
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Non-cell-based: plasmapheresis and charcoalbased hemoabsorption
Cell-based systems : known as bioartificial liver
support systems
Liver support system
Non-cell-based: not improved survival.
Available systems:
molecular adsorbents recirculation system (MARS)
 Cell-based systems: undergoing trial.
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