Immunopathogenesis of viral hepatitis B and C

Abstract

Considerable evidence suggests that immune mechanisms are involved in the pathogenesis of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Both class I-restricted CD8+ T cell and class II-restricted CD4+ T cell responses to viral antigens are important mechanisms that may be responsible for the hepatocyte damage in hepatitis B and C. CD4+ T cell proliferative responses to hepatitis B core antigen (HBcAg) in terms of stimulation index are correlated with hepatitis activity. These responses can be demonstrated in both adult and pediatric patients, and are more vigorous in patients with acute self-limited hepatitis B than in patients with chronic hepatitis B. Patients with hepatitis C also have a significant CD4+ T cell response to HCV antigens. These responses are also more vigorous in acute hepatitis C patients who recover than in patients who evolve to chronic hepatitis. In terms of major histocompatibility complexes (MHC) class I-restricted, CD8+ cytotoxic T lymphocyte (CTL) response, antigenic peptides derived from HBcAg, hepatitis B surface antigen (HBsAg), and polymerase have been demonstrated to be the targets for CTL recognition in hepatitis B patients. Multiple CTL epitopes within HBsAg, HBcAg and polymerase can be detected by sensitizing target cells with synthetic peptides. Likewise, multispecific, HCV-specific CTL responses can coexist with an extensive quasispecies of viral variants. The mechanisms of viral persistence in both hepatitis B and C remain to be clarified.