Immunopathogenesis of hepatitis C virus infection

Abstract

ESOLUTION of acute hepatitis C is generally associR ated with detection of neutralizing antibodies, a high frequency of circulating HCV-specific T cells with a predominant production of Thl cytokines. In contrast, T cell responses in the peripheral blood are usually undetectable in the acute phase of disease and are oriented towards a predominant production of Th2 cytokines when infection becomes chronic. Therefore, different strengths and quality of T cell responses at the early stages of infection may influence the evolution of hepatitis C but the primary causes of these different behaviors are still undefined. A good proportion of patients with long-lasting chronic HCV infection display detectable levels of peripheral blood cytotoxic T lymphocyte (CTL) responses and produce neutralizing anti-envelope antibodies. Moreover, the frequency of intrahepatic HCVspecific CTL seems to be high in these patients, the CTL response is multispecific and the liver environment is characterized by a predominant production of Thl cytokines. Therefore, at this stage of infection the virus appears to have acquired the capacity to escape immune surveillance and to persist in the face of an active antiviral immune response. If these observations derived from in vitro studies actually reflect the strength and the quality of the immune responses in vivo, inhibition of viral replication rather than modulation of the immune response should represent the main objective of anti-HCV therapies once a chronic