Peginterferon alone or with ribavirin enhances HCV-specific CD4⁺ T-helper 1 responses in patients with chronic hepatitis C

Background & Aims: Pegylated interferons (IFNs) with or without ribavirin were shown in several studies to improve sustained virologic response compared with standard IFN α-2 therapy. This study investigated if the greater efficacy of pegylated IFNs might be related to modulation of immunologic responses. Methods: Hepatitis C virus (HCV)-specific CD4+ T-cell responses and cytokine production to various HCV proteins (Elispot assay) in peripheral blood were prospectively assessed in 42 patients receiving IFN α-2a monotherapy, peginterferon (PEG IFN) α-2a monotherapy, or PEG IFN α-2a plus ribavirin and correlated to the outcome of therapy. Results: The sustained virologic response rate was significantly higher in the PEG IFN groups (42% in PEG IFN α-2a monotherapy and 57% in PEG IFN α-2a/ribavirin combination) than in the standard IFN α-2a group (14%). The sustained response was 48% in HCV genotype 1 patients treated with PEG IFN α-2a/ribavirin therapy. Pretreatment HCV-specific CD4+ responses were either weak or absent. PEG IFN alone or combined with ribavirin induced significant increase in the frequency, strength, and breadth of HCV-specific CD4+ T-cell responses with type 1 predominance; whereas interferon α-2a monotherapy was associated with lower, fluctuating, short-lived responses. Sustained responders maintained multispecific HCV-specific CD4⁺ T-cell responses with enhanced IFN-γ production. Relapsers and partial responders initially displayed significant HCV-specific CD4⁺ T-cell responses that waned or were lost. Conclusions: The efficacy of PEG IFN α-2a alone or in combination with ribavirin in inducing high rates of sustained virologic response may be owing to the higher efficacy of PEG IFN in induction and maintenance of significant multispecific HCV-specific CD4⁺ T-helper 1 responses.