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  • Review Article
  • Published:

Treatment decisions and contemporary versus pending treatments for hepatitis C

Nature Reviews Gastroenterology & Hepatology volume 10, pages 713–728 (2013)Cite this article

Subjects

Key Points

  • Response to interferon treatment is associated with an improvement in all-cause mortality in patients with chronic hepatitis C

  • First-generation protease inhibitors improve response rates in patients with genotype 1 infection

  • Although the toxicity of first-generation protease inhibitors plus interferon and ribavirin treatment is acceptable in patients without cirrhosis, treatment might be associated with substantial morbidity, particularly in at-risk groups

  • Mortality from chronic hepatitis C is increased in patients with cirrhosis; unfortunately, treatment responses remain suboptimal in this group

  • The advent of potent interferon-sparing and interferon-free regimens must be considered when weighing up treatment considerations; the stage of disease and likely years gained from a sustained virologic response should be considered

  • Stratification of patients on the basis of stage of disease, potential gain from treatment, likelihood of response and risk of adverse events is required in all groups of patients; patient expectations will need management

Abstract

The primary aim of antiviral therapy for chronic hepatitis C (CHC) is the prevention of progressive disease. A response to interferon (IFN) treatment is associated with an improvement in all-cause mortality and liver-related mortality from hepatitis C. Unless contraindicated, patients with CHC are thus potential candidates for treatment. Improved response rates are observed in patients with HCV genotype 1 infection treated with first-generation protease inhibitors. However, treatment with current first-generation protease inhibitors and IFN is complex and can result in appreciable adverse effects. The advent of potent, pan-genotypic all-oral direct-acting antiviral (DAA) regimens necessitates a critical examination of the immediate application of PEG-IFN, ribavirin and DAA regimens in patients with CHC. Current guidelines and position statements do not make clear recommendations, and are behind the emerging data. Some aspects of the conundrums facing physicians and patients are summarized in this Review. Cirrhosis presents an immediate threat of disease, and ideally treatment should be targeted at those patients who have advancing or advanced disease; unfortunately, a disparity exists, as response rates are reduced in patients with cirrhosis and the risks of adverse events are increased. On balance, patients with mild disease could consider deferring treatment.

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Figure 1: Effect of IFN-sparing or IFN-free regimens on future treatment options for hepatitis C.

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  1. UCL Institute for Liver and Digestive Health, Royal Free London NHS Foundation Trust, Rowland Hill Street, NW3 2PF, London, UK

    Paul M. Trembling, Sudeep Tanwar, William M. Rosenberg & Geoffrey M. Dusheiko

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P. M. Trembling and S. Tanwar have both received educational grant support from Janssen, MSD, Gilead Sciences, Novartis and Roche. W. M. Rosenberg is CEO of iQur Ltd and receives grant funding from Siemens Healthcare Diagnostics Inc. He has speaker bureau roles for Roche and Gilead Sciences and is an advisory committee member for Roche, Gilead Sciences, MSD and GlaxoSmithKline. G. M. Dusheiko holds consultancies for Vertex, Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Pharmasett, Novartis, Human Genome Sciences, Pfizer, Roche, Genentech, Schering Plough, MSD and Tibotec.

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Trembling, P., Tanwar, S., Rosenberg, W. et al. Treatment decisions and contemporary versus pending treatments for hepatitis C. Nat Rev Gastroenterol Hepatol 10, 713–728 (2013). https://doi.org/10.1038/nrgastro.2013.163

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