Gastroenterology

Gastroenterology

Volume 146, Issue 5, May 2014, Pages 1176-1192
Gastroenterology

Reviews and Perspectives
Reviews in Basic and Clinical Gastroenterology and Hepatology
New Hepatitis C Therapies: The Toolbox, Strategies, and Challenges

https://doi.org/10.1053/j.gastro.2014.03.003Get rights and content

Therapy for hepatitis C is undergoing a revolution. Several new drugs against the hepatitis C virus (HCV) have reached the market and many others, including direct-acting antivirals and host-targeted agents, are in phase II or III clinical development. All-oral, interferon-free combinations of drugs are expected to cure more than 90% of infections. A vast amount of data from clinical trials are presented regularly at international conferences or released to the press before peer-review, creating confusion in the viral hepatitis field. The goal of this review is to clarify the current stage of HCV therapy and drug development. This review describes the different classes of drugs and their mechanisms and properties, as well as treatment strategies in development, including those that are interferon-based and interferon-free. HCV treatment options that will be available in 2014–2015 are presented for each genotype. A number of unanswered questions and challenges remain, such as how to treat special populations, the role of ribavirin in interferon-free regimens, the role of HCV resistance in treatment failures, and how to best re-treat patients who failed on treatment. Strategic choices, cost issues, HCV screening, and improving access to care in resource-constrained areas also are discussed.

Section snippets

Pegylated IFNα and Ribavirin

Pegylated IFNα will remain the backbone of some HCV treatment strategies in 2014 and 2015, before slowly but definitively disappearing from HCV treatment regimens—at least in areas of the world that will be able to afford the high cost of IFN-free combinations. Ribavirin can be used to increase rates of sustained virologic response (SVR) (ie, rates of infection cure) or to shorten treatment duration without altering the rates of SVR with both pegylated IFNα and IFN-free regimens, because it

Strategies

In 2014 and 2015, new IFN-containing and IFN-free regimens will become available. Starting in 2015 and onward, IFN-containing regimens will be replaced by all-oral, IFN-free therapies, at least in areas of the world where these regimens are approved and their cost is covered.

Unsolved Scientific Questions

A number of unsolved scientific questions remain. They will need to be explored within the next months to years.

Conclusions

The treatment of HCV infection will change dramatically in 2014–2015 and onward. Many unresolved scientific questions will never be answered because new therapeutic approaches will replace existing ones within a short timeframe until the field stabilizes, probably with the next generation of HCV drugs still at the preclinical or early clinical developmental stages. Pragmatic approaches based on careful interpretation of existing data and the generation of small-scale postapproval studies

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    Conflicts of interest Jean-Michel Pawlotsky has received research grants from Gilead Sciences and has served as an advisor for Abbott, Abbvie, Achillion, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Idenix, Janssen, Merck, Novartis, and Roche.

    Funding Jean-Michel Pawlotsky's work is funded by the National Agency for Research on AIDS and Viral Hepatitis (ANRS), the Fondation pour la Recherche Médicale (FRM), the Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris-Est (UPEC).

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