Role Of Fas Ligand In Immunopathogenesis Of Hepatocellular Carcinoma

Chronic hepatitis predisposes patients to the development of hepatocellular carcinoma (HCC), but the relative importance of the immune response in this process has not been established. The pathogenetic mechanisms potentially responsible for HCC during chronic viral hepatitis include deregulation of viral transactivators, insertional activation of cellular proto-oncogenes, and immune-mediated chronic hepatitis, perhaps enhanced by genotoxic chemicals. The current study demonstrates that chronic immune-mediated liver disease can trigger the development of HCC in hepatitis B virus transgenic mice in the absence of other procarcinogenic stimuli. Furthermore, the incidence of HCC was diminished by treatment with neutralizing antibody to Fas ligand (FasL). These results indicate that an antigen-specific, FasL-dependent immune response can initiate and sustain the process of carcinogenesis during chronic viral hepatitis.