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    ACUTE HEPATIC FAILURE

    DEFINITION

    Acute severe impairment of hepatocellular function secondary to
    cytotoxicity or cholestasis. 

    Fulminant hepatic failure refers to acute hepatic failure complicated
    by encephalopathy.

    TOXIC CAUSES

    Intrinsic hepatotoxins
         Acetaminophen (paracetamol)
         Amanita phalloides 
         Arsenic
         Carbon tetrachloride (and other chlorinated hydrocarbons)
         Copper
         Ethanol
         Iron 
         Methotrexate
         Phosphorus

    Idiosyncratic hepatotoxins
         Allopurinol 
         Amiodarone
         Chlorpromazine
         Chlorpropamide 
         Disulfiram 
         Erythromycin estolate
         Gold 
         Haloalkanes: halothane, isofluorane, and enflurane
         Isoniazid
         Ketaconazole 
         Methyldopa 
         Monoamine oxidase inhibitors
         Nitrofurantoin
         Nonsteroidal antiinflammatory drugs
         Phenytoin
         Propylthiouracil 
         Rifampicin
         Sulfonamides
         Tetracycline
         Valproic acid 

    NON-TOXIC CAUSES

    Acute viral hepatitis
    Acute fatty liver of pregnancy
    Autoimmune chronic hepatitis
    Budd-Chiari syndrome and veno-occlusive disease
    Hyperthermia
    Hypoxia

    Malignant infiltration
    Reye's syndrome
    Sepsis 
    Wilson's disease

    CLINICAL FEATURES

    After a variable latent period, anorexia, nausea, vomiting and right
    upper quadrant discomfort may appear.  Increased serum bilirubin
    levels and jaundice may develop reflecting progression of liver
    injury.  Hypoglycaemia, lactic acidosis, coagulopathy and renal
    failure are typical features in severe cases.  Gastrointestinal
    haemorrhage may occur due to decreased synthesis of vitamin
    K-dependent clotting factors.  Lactic acidosis can occur as a result
    of impaired hepatic uptake or metabolism of lactate or increased
    lactate production secondary to tissue hypoxia.

    Severe cases progress to fulminant hepatic failure which is
    characterized by development of  encephalopathy.  Clinical features of
    encephalopathy are central nervous system depression and abnormal
    neuromuscular function (increased muscle tone, myoclonic jerking and
    asterixis).  Potential complications of fulminant hepatic failure
    include cerebral oedema and raised intracranial pressure, and
    intractable hypotentension.

    DIFFERENTIAL DIAGNOSIS

    Chronic hepatic failure
    Haemolysis
    Encephalopathy due to other causes

    RELEVANT INVESTIGATIONS

    Blood glucose
    Renal function
    Serum albumin
    Serum bilirubin 
    Serum electrolytes
    Serum transaminases (ALT/SGPT and AST/SGOT)
    Prothrombin time/INR

    Encephalopathic patients may require CT scan of the head and an EEG.

    TREATMENT

    All agents that may be contributing to hepatotoxicity should be
    immediately discontinued.

    Care is primarily supportive.  Patients developing fulminant hepatic
    failure require intensive supportive management of acute complications
    including encephalopathy, coagulopathy, electrolyte and acid-base
    disturbances, renal failure, sepsis and cerebral oedema.

    Administration of intravenous  n-acetyl cysteine is indicated in
    acute hepatic failure from acetaminophen poisoning.

    CLINICAL COURSE AND MONITORING

    In patients who do not develop encephalopathy, complete recovery is
    the rule.  Serum transaminases, INR, bilirubin, renal function and
    fluid balance should be carefully monitored until clinical improvement
    is noted.

    Development of fulminant hepatic failure is associated with extremely
    high acute mortality, even with aggressive intensive medical care. 
    Timely hepatic transplantation may be life-saving in certain
    individuals.  However, survivors of fulminant hepatic failure will
    generally have a complete recovery with restoration of hepatic and
    structure and function usual by 6 to 10 weeks.

    LONG-TERM COMPLICATIONS

    Not usual.

    AUTHOR(S)/REVIEWERS

    Author:        Dr. Maria Cristina Alonzo M.D.
                   Dept.of Environmental Health and Chemical Safety
                   Ministry of Health 
                   Avda. 18 de Julio 1892 4to. piso anexo B
                   Montevideo, Uruguay.

    Reviewers:     Birmingham 3/99:  T. Meredith, L. Murray, A. Nantel, J.
                   Szajewski.