Fulminant viral hepatitis: molecular and cellular basis, and clinical implications

Abstract

Fulminant hepatic failure is defined by the sudden onset of severe liver injury accompanied by hepatic encephalopathy in an individual who previously had no evidence of liver disease. This disease causes multiple organ failure and is associated with a high mortality. The most frequently recognised cause of fulminant or subfulminant hepatic failure is viral hepatitis. Data are now emerging to support the hypothesis that, irrespective of the aetiology of fulminant hepatic failure, the host's immune response (including production of proinflammatory cytokines and mediators) contributes to microcirculatory disturbances that result in hypoxic injury and cell death (apoptosis). Impairment of the scavenger function of the reticuloendothelial cell system further contributes to reduced hepatic blood flow and ischaemic necrosis. An increased understanding of the molecular pathogenesis of fulminant hepatic failure now enables new molecular therapeutic modalities to be tested. Given the complexity of this multi-dimensional disorder, the challenge is to provide a rational basis for treatment. This might include enhancement or suppression of immune responsiveness by manipulation of endogenous cytokine synthesis or by cytokine administration and, at the same time, use of strategies to increase hepatic regeneration.