Editors' Choicehepatitis C

A One-Two Punch to the Hepatitis C Virus

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Science Translational Medicine  01 Feb 2012:
Vol. 4, Issue 119, pp. 119ec16
DOI: 10.1126/scitranslmed.3003772

Transmitted by infected blood, the hepatitis C virus (HCV) affects 180 million people around the world. HCV is a leading cause of chronic liver disease and can lead to liver cancer. The conventional therapy for HCV—injections of the antiviral drug interferon-α—is not well tolerated because of the severe side effects. In a proof-of-principle demonstration, Lok et al. combined two direct-acting, antiviral oral medications, daclatasvir (a first-in-class inhibitor of HCV replication) and asunaprevir (an HCV protease inhibitor), to achieve a sustained virologic response in some patients who had not responded to previous HCV treatment.

This phase IIa multicenter, open-label study explored the safety and efficacy of the dual administration of daclatasvir and asunaprevir. Twenty-one patients with hepatitis C-genotype 1, who had been refractory to previous therapy, were randomly assigned in equal ratio to Group A, in which 11 patients received therapy with daclatasvir and asunaprevir, or to Group B, in which 10 patients received quadruple therapy with daclatasvir, asunaprevir, and the standard treatment (peginterferon α-2a plus ribavirin). During the 24-week treatment, there were no serious adverse events, no deaths, and no treatment discontinuations due to adverse events.

All 10 patients in Group B on the four-drug regimen experienced a sustained virologic response and showed undetectable virus at the end of treatment and 12 weeks beyond. At week 24, 9 of these 10 patients maintained their response. Thus, infected individuals who had previously been unresponsive to HCV therapy were able to achieve a sustained response on the four-drug combination. In the other treatment arm, 4 of the 11 patients in Group A receiving only the two-drug antiviral regimen also had undetectable levels of the HCV in their blood 12 and 24 weeks after treatment ended. The most exciting message of this study is that attenuation of a hepatitis C infection may be achieved without interferon or ribavirin. These encouraging results promise to significantly advance HCV therapy and suggest that future cures for patients unresponsive to traditional treatments may be in the cards.

A. S. Lok et al., Preliminary study of two antiviral agents for hepatitis C genotype 1. N. Engl. J. Med. 366, 216–224 (2012). [Abstract]

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