Apoptosis and viral hepatitis

In chronic viral hepatitis, necrosis is the central histologic feature. However, cells also die by apoptosis. The cytotoxic T lymphocyte (CTL) plays a central role in both mechanisms of cell death. Necrotic cell death occurs in response to an injurious stimulus, whereas apoptosis also plays a role in physiologic cell death. In contrast to necrosis, when cells die by apoptosis they form apoptotis bodies without the release of toxic intracellular contents. In viral hepatitis, apoptosis is increased and correlates with the degree of histologic inflammation, Interaction between the CTL and the hepatocyte signals apoptosis, and this interaction occurs through the release of intracellular proapoptotic agents and via ligand/receptor interaction. Viral gene products may also act to induce or inhibit apoptosis. Irrespective of the pathway, the apoptotic cascade is activated and proceeds through enzymes known as caspases. In the liver, apoptosis is not restricted to the hepatocyte, and non-parenchymal apoptosis may be important in fibrogenesis. We review the essential features of apoptosis and how they relate to parenchymal and non-parenchymal cell injury in viral hepatitis. Potential future pro-and anti-apoptotic agents may be targets for therapy.