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

Objective To assess the efficacy and safety of interferon alfa with or with out ribavirin for treatment of chronic hepatitis C. Design Systematic review of randomised trials on interferon alta plus ribav irin combination therapy versus interferon alfa. Patients were naive (not p reviously treated with interferon), relapsers (transient response to previo us interferon therapy), or non-responders (no response to previous interfer on therapy). Studies reviewed Of 1155 references identified, 48 trials with 6585 patient s met the inclusion criteria. Patients were followed to the end of treatmen t 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 n ot having a sustained virological response for 6 months by 26% in naive pat ients (relative risk 0.74, 95% confidence interval 0.70 to 0.78), 33% in re lapsers (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 comb ination therapy (Peto odds ratio 0.45, 0.19 to 1.06). Combination therapy s ignificantly, reduced the risk of not having improvement in results of hist ology 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 discontinua tions 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.