Acute liver failure of unknown pathogenesis: the hidden agenda.

A major proportion of sporadic cases of ALF remain of uncertain cause (formerly termed NANB hepatitis). The application of sensitive molecular biology techniques such as PCR indicates that a few cases may be due to cryptic infections with one or more known hepatotropic agents, such as HBV and HCV. Evidence continues to accumulate to incriminate at least one potentially novel and transmissible agent (candidate hepatitis F). In ALF of unknown pathogenesis, survival without transplantation remains less than 20% despite recent improvements in medical management. Close study of recurrent hepatitis after grafting may provide further clues to the possible causes of ALF and the interaction between infectious agent and host. The continued pursuit of potential causes seems justified to allow stratification according to possible pathogeneses. This scientific approach should provide a rational basis for future therapeutic options.