Ribavirin for chronic hepatitis C: and the mystery goes on

Twenty years ago, ribavirin was first used in the treatment for chronic hepatitis C. After few years, ribavirin, in combination with interferon-alpha, showed a dramatic synergistic efficacy against hepatitis C virus infection, leading to viral clearance in about 50% of patients. Recent discovery of potent inhibitors of hepatitis C virus proteases did not replace ribavirin as the mainstay of combination therapy for chronic hepatitis C. Despite this fundamental role of ribavirin, many aspects of the mechanism of action and of the optimal dose and duration of therapy remain to be discovered or settled. In the present review, the authors recall the milestones in the history of ribavirin and try to shed light on the more relevant features of ribavirin action and utilization, and on the clinical problems encountered in managing and optimizing treatment for chronic hepatitis C. Finally, some potential off-label use of this drug in most difficult-to-treat subjects is pointed out. In conclusion, even if a sort of mystery surrounds ribavirin, its efficacy against hepatitis C virus infection fortunately remains lasting and stable.