Duration of peginterferon therapy in acute hepatitis C: a randomized trial.

Spontaneous resolution of acute hepatitis C virus infection cannot be predicted, and chronic evolution of the disease occurs in a majority of cases. To assess the efficacy and safety of peginterferon alpha-2b administered for 8, 12, or 24 weeks in patients with acute hepatitis C virus infection a total of 161 patients were identified with acute hepatitis C virus infection. Of these, 30 patients refused treatment but were retained in the study as a nonrandomized comparison group. Of the 131 patients who consented to treatment, 29 patients spontaneously resolved, leaving 102 patients randomly assigned to peginterferon alpha-2b (1.5 microg/kg) for 8 weeks (group A; n=34), 12 weeks (group B; n=34), and 24 weeks (group C; n=34). The primary end point was sustained virologic response. An intent-to-treat analysis was used for efficacy and safety end points. Sustained virologic response was achieved in 23/34 (67.6%), 28/34 (82.4%), and 31/34 (91.2%) of patients in groups A, B, and C, respectively; all had undetectable hepatitis C virus RNA 48 weeks after the end of therapy. Treatment for 8 or 12 weeks was effective in genotypes 2, 3, and 4, whereas genotype 1 required 24 weeks of therapy. The 8- and 12-week regimens were associated with fewer adverse events compared with the 24-week regimen. In conclusion, peginterferon alpha-2b effectively induces high sustained virologic response rates in patients with acute hepatitis C virus infection, thus preventing development of chronic hepatitis C. Duration of treatment should be further optimized based on genotype and rapid virologic response at week 4.

Pegylated interferon alpha therapy in acute hepatitis C: relation to hepatitis C virus-specific T cell response kinetics.

Pegylated interferon alpha (PEG IFN-alpha) improves sustained virological response rates in chronic hepatitis C, but neither its role in acute hepatitis C nor the biologic basis for its action has been defined. This prospective study assessed the efficacy of PEG IFN-alpha treatment in acute hepatitis C in relation to the kinetics of hepatitis C virus (HCV)-specific CD4(+) T cell responses during therapy and follow-up. Forty subjects with proven acute hepatitis C who received either PEG IFN-alpha plus ribavirin (n = 20) or PEG IFN-alpha monotherapy (n = 20) for 24 weeks in addition to 14 untreated subjects with acute hepatitis C were prospectively followed. Serum HCV RNA, HCV-specific CD4(+) T cell responses, and cytokine production were measured before and during therapy and at follow-up and correlated to the outcome. The sustained virological response rate was 85% with PEG IFN-alpha/ribavirin combination and 80% with PEG IFN-alpha monotherapy. Five untreated subjects had spontaneous recovery. The frequency, magnitude, and breadth of HCV-specific CD4(+) T helper 1 responses were significantly higher in treated subjects compared with untreated subjects with self-limited disease or subjects with chronic evolution. The CD4(+) T cell responses were maintained in subjects with sustained virological responses and self-limited disease but fluctuated in those who developed chronic infection. In conclusion, PEG IFN-alpha therapy in acute hepatitis induces high rates of sustained virological response and prevents choronicity, probably through efficient early stimulation of multispecific HCV-specific CD4(+) T helper 1 responses.

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 alpha-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 alpha-2a monotherapy, peginterferon (PEG IFN) alpha-2a monotherapy, or PEG IFN alpha-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 alpha-2a monotherapy and 57% in PEG IFN alpha-2a/ribavirin combination) than in the standard IFN alpha-2a group (14%). The sustained response was 48% in HCV genotype 1 patients treated with PEG IFN alpha-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 alpha-2a monotherapy was associated with lower, fluctuating, short-lived responses. Sustained responders maintained multispecific HCV-specific CD4+ T-cell responses with enhanced IFN-gamma 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 alpha-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.