Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b

World J Gastroenterol. Dec 14, 2017; 23(46): 8120-8127
Published online Dec 14, 2017. doi: 10.3748/wjg.v23.i46.8120

Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b
Tatsuo Kanda, Kazushige Nirei, Naoki Matsumoto, Teruhisa Higuchi, Hitomi Nakamura, Hiroaki Yamagami, Shunichi Matsuoka, Mitsuhiko Moriyama

Abstract

The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1b (GT1b) is founded in 70% of HCV-infected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1b-infected patients with treatment failure.

Core tip: In this minireview, we focused on the retreatment of patients with treatment failure of direct-acting antiviral agents against hepatitis C virus genotype 1b (HCV GT1b) infection. We summarized the retreatment regimens for patients with failure of peginterferon and ribavirin plus HCV NS3/4A inhibitors and for those with failure of HCV NS5A inhibitors. We also demonstrated the resistance-associated substitutions of HCV NS5B nucleos(t)ide inhibitors. Attention should be paid when selecting both the initial treatment and retreat regimens to completely eradicate HCV infection.

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Retreatment regimens for patients with hepatitis C virus infection for whom the initial combination of direct-acting antivirals has failed.

DAAs: Direct-acting antivirals; HCV GTs: Hepatitis C virus genotypes; RAS: Resistance-associated variants; N/A: Not available.