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  • Review Article
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Novel therapies for hepatitis C — one pill fits all?

Nature Reviews Drug Discovery volume 12, pages 595–610 (2013)Cite this article

Subjects

Key Points

  • Hepatitis C is the only chronic viral infection that can be cured through drug therapy.

  • The current standard of care in chronic hepatitis C virus (HCV) infection is pegylated interferon plus ribavirin with the addition of a protease inhibitor in genoytpe 1 infection.

  • Numerous novel direct-acting antiviral (DAA) drugs are in advanced clinical development and are anticipated to reach the market within the next few years.

  • Advanced novel DAAs target various HCV factors: the NS3/4A protease, the NS5A RNA binding protein and the NS5B RNA-dependent RNA polymerase

  • Sustained virological response or cure of HCV infection is possible using all-oral combinations of DAAs.

  • Nucleoside and nucleotide inhibitors of the NS5B polymerase usually have a high barrier to resistance and good activity against different HCV genotypes and thus are likely candidates as backbone drugs in future all-oral regimens.

Abstract

Almost 25 years after the hepatitis C virus (HCV) was identified, and following intense research and development efforts, a large number of direct-acting antiviral drugs are now beginning to reach patient care. Accordingly, the way in which care is delivered is evolving at a breath-taking pace. Here, we review the current and upcoming treatment options for HCV, describe the key challenges facing clinicians and drug developers and discuss how the landscape in the HCV arena will change over the coming years.

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Figure 1
Figure 2: Evolution of treatment of HCV.
Figure 3: Molecular biology and drug targets in HCV.
Figure 4: Selection of anti-HCV drugs in advanced development.

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Acknowledgements

The authors are supported by the German Center for Infection Research (DZIF) and Hep-Net, the German network of competence on viral hepatitis, which is a project of the German Liver Foundation. The authors thank S. Ciesek for critical reading of the manuscript and S. Hardtke for editorial support.

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  1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl Neuberg Strasse 1, Hannover, 30625, Germany

    Michael P. Manns & Thomas von Hahn

  2. Institute for Molecular Biology, Hannover Medical School, Carl Neuberg Strasse 1, Hannover, 30625, Germany

    Thomas von Hahn

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Correspondence to Michael P. Manns.

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Competing interests

M.P.M has received fees for consulting work and/or for giving lectures from Roche, Bristol-Myers Squibb, Gilead, Boehringer Ingelheim, Novartis, Merck, Janssen, GlaxoSmithKline, Idenix and Achillion. He has also received research grants from Roche, Gilead, Novartis, Boehringer Ingelheim, Bristol-Myers Squibb, Merck and Janssen. T.v.H. has received speaker's fees from Bristol-Myers Squibb, Merck Sharp & Dohme, and research funding from Novartis and Roche.

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Manns, M., von Hahn, T. Novel therapies for hepatitis C — one pill fits all?. Nat Rev Drug Discov 12, 595–610 (2013). https://doi.org/10.1038/nrd4050

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