ACUTE HEPATIC-FAILURE

Fulminant hepatic failure (FHF) is defined as hepatic encephalopathy d eveloping within 8 weeks of the onset of symptoms in a patient with a previously healthy liver, whereas when hepatic encephalopathy develops between 8 and 24 weeks after the onset of the syndrome it is called s ubmassive hepatic necrosis (SHN). Hepatic encephalopathy is divided in to clinical grades, Grade I-IV, in order of severity. Progression to m ore severe grades of encephalopathy (Grade III or IV) is a serious pro gnostic development and indicates that the patient has a high risk of dying. FHF and SHN are always associated with a severe coagulopathy. F HF or SHN may be caused by viral hepatitis (HAV, HBV, HDV, and HEV); m etabolic disease (Wilson's); toxins and rare causes such as acute fatt y liver of pregnancy, Reye's syndrome or lymphoma. Acetaminophen (eith er taken alone in large doses or in combination with ethanol), phenyto in and volatile anaesthetics are important causes of drug-induced FHF. SHN is less commonly drug-related. Extremes of age (< 10, > 40 years) , drugs other than acetaminophen, delayed development of encephalopath y after the onset of jaundice and the absence of an identifiable cause of hepatic injury are poor prognostic factors for spontaneous recover y to FHF. SHN invariably carries a poor prognosis. Cerebral oedema lea ding to raised intracranial pressure is a common mode of death in both conditions. Clinical management is directed to: (1) correcting metabo lic disturbances, e.g. hypoglycaemia, (2) avoiding renal failure, (3) monitoring and treating elevations in intracranial pressure, (4) treat ing infection, (5) giving an antidote (e.g. N-acetylcysteine) to the o ffending toxin (e.g. acetaminophen). Up to recently, orthotopic liver transplantation (OLT) offered the only hope to patients with FHF or SH N who were deteriorating despite maximal medical treatment. Results in dicate approximately 65% 1-year survival after OLT for FHF. Recently, alternatives to OLT have been developed including temporary heterotopi c partial liver grafting or extracorporeal perfusion through columns c ontaining hepatocytes. How these new modalities will impact on managem ent of FHF and SHN remains to be determined.