Apoptosis and pathogenesis of viral hepatitis C--an update

Hepatitis C virus is a major causative agent of chronic liver disease. Viral genotype, mutations, virus-host interaction, expression of viral proteins and host immune-reaction are important factors in the pathogenesis of HCV infection. Precise pathogenesis and perpetuation of hepatocellular injury in hepatitis C viral infection remain unclear. Proposed mechanisms include direct viropathic effect, the host immune response mediated through cytotoxic T lymphocytes, both viropathic and cytopathic effects, and macrophages/monocytes. Apoptosis occurs both in acute or chronic hepatitis and has been suggested to be mediated through Fas antigen. In HCV infection, Fas expression is up-regulated in the liver cells in line with the severity of liver inflammation. When HCV-specific T cells migrate into hepatocytes and recognize the viral antigen via the T cell receptor, they become activated and express Fas ligand that transduces the apoptotic death signal to Fas-bearing hepatocytes resulting in their destruction. Thus, the Fas system plays an important role in liver cell injury by HCV infection. Possible inducers of apoptosis in hepatitis C include cytokines, especially tumor necrosis factor-alpha (TNF-alpha), released by inflammatory cells, and acting through TNF and other cytokine receptors.