Interferon-free hepatitis C treatment: one pill to fit all?

HCV News LogoHepatitis C virus (HCV) treatment is evolving rapidly. Less than 10 years ago, few individuals could be successfully treated. Now, more than two-thirds of eligible treatment-naive patients are effectively cured with a combination of pegylated interferon and ribavirin, and addition of a first-generation protease inhibitor for those with HCV genotype 1 infection (1, 2).

Yet all licensed regimens involve weekly injections and a high pill burden; adverse effects are common and include substantial mental illness and cytopenias (3). Patients with advanced liver disease or those who have had previously unsuccessful treatment have more severe side-effects and a lower chance of cure. Consequently, many individuals are deemed ineligible for or dissuaded from treatment by their medical practitioners, and are left to wait and hope for less toxic treatments to become available.

In The Lancet, Eric Lawitz and colleagues (4) report findings from their phase 2 trial of the efficacy and safety of a fixed-dose, single-pill combination of sofosbuvir (an HCV NS5B polymerase inhibitor) and ledipasvir (an HCV NS5A inhibitor), with or without ribavirin. This was an open-label, randomised study of 100 patients with HCV genotype 1a or 1b. The investigators included both treatment-naive patients (cohort A, n=60) and previous virological non-responders or relapsers to first-generation protease inhibitor with pegylated interferon plus ribavirin (cohort B, n=40). 22 (55%) of the 40 participants in cohort B had compensated cirrhosis. Treatment-naive individuals were randomly allocated to receive sofosbuvir plus ledipasvir alone for 8 weeks (n=20) or 12 weeks (n=19), or sofosbuvir plus ledipasvir plus ribavirin for 8 weeks (n=21). Treatment-experienced patients received either 12 weeks of sofosbuvir plus ledipasvir alone (n=19) or with ribavirin added (n=21).

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