Hepatitis C virus-specific T-cell reactivity during interferon and ribavirin treatment in chronic hepatitis C

Background & Aims: The role of virus-specific T-helper lymphocyte reactivit y in determining the therapeutic response in chronic hepatitis C virus (HCV ) infection is not fully understood. Methods: We studied CD4(+) T lymphocyt e proliferation together with interferon (IFN)-gamma and interleukin (IL)-1 0 production from peripheral blood mononuclear cells in response to 4 HCV a ntigens (core, NS3, NS4, and NS5) in 25 patients with chronic hepatitis C u ndergoing antiviral therapy with IFN alone or in combination with ribavirin , prospectively, before, during, and after treatment. Results: HCV-specific T-cell reactivity was uncommon at baseline but increased markedly during a ntiviral therapy, peaking around treatment weeks 4-8. Resolution of hepatit is C viremia was significantly more likely in patients who developed HCV-sp ecific T-cell proliferation with increased IFN-gamma production. The main d ifference in T-cell reactivity of patients treated with IFN plus ribavirin was a significantly lower production of IL-10, whereas lymphocyte prolifera tion was similar to that in patients receiving IFN monotherapy, Conclusions : Treatment-induced control of hepatitis C viremia is associated with the d evelopment of HCV-specific T-cell responses with enhanced IFN-gamma and low IL-10 production. The greater efficacy of combination therapy with IFN-alp ha plus ribavirin may be related to its ability to suppress HCV-specific IL -10 production.