Classification, etiology, and considerations of outcome in acute liver failure.

Clinical descriptions of fulminant hepatic failure as originally reported, along with the subgroups of subfulminant and late onset hepatic failure identified later, are considered in relation to the proposed new classification of hyperacute, acute, and subacute liver failure. This reflects different clinical patterns of illness, etiology, and most importantly, prognosis. In addition to the defining state of encephalopathy and other manifestations directly related to the severe derangement in function and structure of the liver, the constellation of clinical symptoms and signs in acute liver failure (ALF) includes, to varying degrees, those of multiorgan failure. The latter develops because of tissue hypoxia from microcirculatory changes consequent on endotoxemia, and activation of macrophages and release of cytokines as a result of secondary bacteria infection due to an early failure of host defenses to infection in ALF. Paracetamol overdose-the commonest cause of acute liver failure in the United Kingdom-is increasing in frequency in other Western countries, but fulminant viral hepatitis is the most frequent etiology worldwide. Marked geographical variations are seen in the frequency with which the viral types A to E are implicated. Whereas hepatitis C is the major cause of ALF in Japan and the Far East, fulminant hepatitis C is seen rarely in America and European countries where most series show that in about one third of cases of presumed viral ALF, no specific agent can be identified. Over the past 10 years, the survival of those with grade 3 to 4 encephalopathy has shown a steady rise as a result of improvements in medical care, quite apart from the introduction and now widespread availability of transplantation for the treatment of this condition. As shown by a number of groups, a variety of different hematologic, biochemical, and clinical features can be used as predictive indices of the likely outcome and in determining the approach to treatment.