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.