title: Interferon-α/β for treatment of chronic hepatitis C infection in the era of direct-acting antiviral agents.
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 (DAA) will be approved soon for genotype 1 patients. Here, we discuss the role of IFN-α/β in the forthcoming "era of DAA" with consideration of limitations and concerns about IFN-free therapies. First, the therapeutic efficacy of first-generation DAA varies among the different subtypes. While the rate of sustained virological 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 DAA. Second, there is concern about the emergence of drug-resistance resulting from inappropriate use of DAA. The clinical significance of pre-existing resistant variants has not been elucidated. Drug resistance may affect the efficacy of next-generation treatments. An IFN and ribavirin backbone in combination with DAA is an effective measure to prevent the emergence of drug resistance and/or to suppress pre-existing 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 DAA, low-dose IFN maintenance therapy is a treatment option until the next-generation therapy with pan-genotypic potency and high genetic barrier become available.
authors: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Masaru
authors: M
authors: Enomoto
authors: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Akihiro
authors: A
authors: Tamori
authors: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Yoshiki
authors: Y
authors: Murakami
authors: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Norifumi
authors: N
authors: Kawada
keywords: direct-acting antiviral agents; drug resistance; genotype; hepatitis C virus; interferon