Liver Failure

Mackay Memorial Hospital Department of Internal Medicine Division of Gastroenterology R4

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, S268S273

 Acetaminophen

toxicity Idiosyncratic drug toxicity Hepatotropic viruses Miscellaneous causes Indeterminate acute liver failure (viruses can not be demonstrated ? )

Uncommon causes: Wilsons 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

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

Respiratory failure (ARDS): mechanical ventilation. Renal failure (hypovolemia, hepatorenal syndrome, ATN): hemodynamic monitor, central pressure, volume repletion, avoid nephrotoxic agent

Encephalopathy

major complication precise mechanism remains unclear Hypothesis: Ammonia production Treatment toward reducing ammonia production Watch out airway, prevent aspiration

Encephalopathy

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

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

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.

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

Specific 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

Wilsons 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

Liver transplant

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 Kings 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.

Liver transplant

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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

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

Liver support system

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.