Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of randomised trials

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Abstract
Objective: To assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C. Design: Systematic review of randomised trials on interferon alfa plus ribavirin combination therapy versus interferon alfa. Patients were naive (not previously treated with interferon), relapsers (transient response to previous interferon therapy), or non-responders (no response to previous interferon therapy). Studies reviewed: Of 1155 references identified, 48 trials with 6585 patients met the inclusion criteria. Patients were followed to the end of treatment in 20 trials and in 28 trials for 12–96 weeks after treatment. Main outcome measures: Virological response and morbidity plus mortality. Results: Compared with interferon, combination therapy reduced the risk of not having a sustained virological response for 6 months by 26% in naive patients (relative risk 0.74, 95% confidence interval 0.70 to 0.78), 33% in relapsers (0.67, 0.57 to 0.78), and 11% in non-responders (0.89, 0.83 to 0.96). Morbidity and mortality showed a non-significant trend in favour of combination therapy (Peto odds ratio 0.45, 0.19 to 1.06). Combination therapy significantly reduced the risk of not having improvement in results of histology by 17% in naive patients (0.83, 0.74 to 0.93) and by 27% in relapsers and non-responders (0.73, 0.66 to 0.82). The risk of treatment discontinuations was significantly higher after combination therapy (1.28, 1.07 to 1.52). Conclusion: Treatment with interferon alfa plus ribavirin has a significant beneficial effect on the virological and histological responses of patients with chronic hepatitis C, irrespective of previous treatment. Combination therapy may therefore also be considered appropriate for relapsers and non-responders. What is already known on this subject Interferon alfa was the recommended treatment for chronic hepatitis C until the late 1990s Combination therapy is recommended for previously untreated patients with chronic hepatitis C, but the benefit of treating relapsers and non-responders to previous treatment with interferon remains controversial The effect of treatment on liver related morbidity and mortality has not been established What this study adds Combination therapy is more effective in treating hepatitis C than interferon alfa alone in naive patients, relapsers, and non-responders Combination therapy significantly reduced the risk of not having a sustained virological or histological response irrespective of previous treatment and may therefore also be considered in relapsers and non-responders to previous treatment The data indicate a non-significant trend towards a beneficial effect on morbidity plus mortality rates