The beginning of the end: what is the future of interferon therapy for chronic hepatitis C?

Interferon has been the backbone of therapy for hepatitis C virus (HCV) infection for over 20years. Initial response rates were poor, however they have slowly but steadily improved, such that with the addition of the nucleotide analogue ribavirin and the pegylation of interferon, over 50% of infected individuals could be cured with a course of therapy. However, interferon therapy is not ideal, requiring up to a year of weekly injections and associated with numerous systemic side effects. Advances in understanding of the HCV lifecycle have led to the development of numerous highly effective, well-tolerated oral direct acting antivirals (DAAs). Although the first DAAs were combined with peginterferon and ribavirin, with the rapid progress in the field, it is likely that interferon-free therapy will be available for most patients in the relatively near future. In the short term, peginterferon will be required with either the protease inhibitor simeprevir, or the nucleotide analogue polymerase inhibitor, sofosbuvir, for the treatment of genotype 1 infection. Peginterferon also appears to be a useful adjunct to sofosbuvir and ribavirin for patients with genotype 3 infection, particularly those with cirrhosis. In the future, once combination DAA therapies are available, peginterferon will serve a smaller and smaller role. Peginterferon may be useful as part of QUAD therapy with 2 DAAs and ribavirin in prior null responders or in patients who fail DAA regimens with multi-drug resistant HCV. Peginterferon may also have a role in resource-limited regions to reduce the number and/or duration of DAAs required. Ultimately, although peginterferon will remain a salvage therapy, its days as a mainstay of therapy are definitely numbered.