December 12, 2013

Hepatology Research

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Review Article

Masaru Enomoto*, Akihiro Tamori, Yoshiki Murakami, Norifumi Kawada

DOI: 10.1111/hepr.12289

This article is protected by copyright. All rights reserved.

Publication History
Accepted manuscript online: 11 DEC 2013 08:23PM EST
Manuscript Accepted: 6 DEC 2013

Keywords: DAA; direct-acting antiviral agents;  HCV;  hepatitis C;  IFN;  interferon

Abstract

Type I interferons (IFN-α/β), with or without ribavirin, have been the only agents that can eradicate the hepatitis C virus (HCV). An IFN-free regimen combining oral direct-acting antiviral agents (DAAs) will be approved soon for genotype 1 patients. Here we discuss the role of IFN-α/β in the forthcoming “era of DAAs” with consideration of limitations and concerns about IFN-free therapies. First, the therapeutic efficacy of first-generation DAAs varies among the different subtypes. While the rate of sustained virologic response (SVR) is 60–90% among patients with genotype 1b, the rate often falls short of 50% in patients with genotype 1a. IFN and ribavirin can still be indicated for patients with genotype 1a as a platform for combination with DAAs. Second, there is concern about the emergence of drug-resistance resulting from inappropriate use of DAAs. The clinical significance of preexisting resistant variants has not been elucidated. Drug resistance may affect the efficacy of next-generation treatments. An IFN and ribavirin backbone in combination with DAAs is an effective measure to prevent the emergence of drug resistance and/or to suppress preexisting resistant viruses. Third, it remains unknown whether the incidence of hepatocellular carcinoma (HCC) will be reduced in patients who achieve SVR with IFN-free regimens. In contrast, there are many reports in Japan demonstrating the preventive effects of IFN on the development of HCC. When patients do not achieve SVR with first-generation DAAs, low-dose IFN maintenance therapy is a treatment option until the next-generation therapy with pangenotypic potency and high genetic barrier becomes available.

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