Does tumor necrosis factor play a role in the pathogenesis of fulminant hepatitis?

Fulminant hepatitis is associated with an 80% mortality rate. Surviving patients do not develop chronic liver disease. Failure to produce adequate amounts of interferon and to achieve an antiviral state seem to be the basic defects in this condition. Tumor necrosis factor (TNF) has been shown to be induced by viruses. By rapid lysis of virus infected cells, it also prevents optimal viral replication thus reducing the viral yield and the infection rate and extent. On the other hand, it has growth promoting characteristics. We postulate that TNF has a dual role in fulminant hepatitis: (a) It acts as an antiviral agent by eliminating virus infected cells thus reducing viral yields and limiting spread of infection; (b) it may be the signal for hepatocyte regeneration. Only those patients, in whom the regeneration rate exceeds lysis of infected hepatocyte by TNF, survive.