Fulminant hepatic failure (FHF) is defined as hepatic encephalopathy developing 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 submassive hepatic necrosis (SHN). Hepatic encephalopathy is divided into clinical grades, Grade I-IV, in order of severity. Progression to more severe grades of encephalopathy (Grade III or IV) is a serious prognostic development and indicates that the patient has a high risk of dying. FHF and SHN are always associated with a severe coagulopathy. FHF or SHN may be caused by viral hepatitis (HAV, HBV, HDV, and HEV); metabolic disease (Wilson's); toxins and rare causes such as acute fatty liver of pregnancy, Reye's syndrome or lymphoma. Acetaminophen (either taken alone in large doses or in combination with ethanol), phenytoin 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 encephalopathy after the onset of jaundice and the absence of an identifiable cause of hepatic injury are poor prognostic factors for spontaneous recovery to FHF. SHN invariably carries a poor prognosis. Cerebral oedema leading to raised intracranial pressure is a common mode of death in both conditions. Clinical management is directed to: (1) correcting metabolic disturbances, e.g. hypoglycaemia, (2) avoiding renal failure, (3) monitoring and treating elevations in intracranial pressure, (4) treating infection, (5) giving an antidote (e.g. N-acetylcysteine) to the offending toxin (e.g. acetaminophen). Up to recently, orthotopic liver transplantation (OLT) offered the only hope to patients with FHF or SHN who were deteriorating despite maximal medical treatment. Results indicate approximately 65% 1-year survival after OLT for FHF. Recently, alternatives to OLT have been developed including temporary heterotopic partial liver grafting or extracorporeal perfusion through columns containing hepatocytes. How these new modalities will impact on management of FHF and SHN remains to be determined.
