Identification of Genotype 2 HCV in Serotype-1 Hepatitis C Patients Unresponsive to Daclatasvir plus Asunaprevir Treatment

Abstract

It is important to determine the genotypes or serotypes of hepatitis C virus (HCV) in patients before treatment with direct-acting antiviral agents (DAAs), because the effects of DAAs differ among genotypes. In Japan, two tests for HCV typing are available clinically, but only serotyping, not genotyping, is approved by the public health insurance. Although most serotype-1 Japanese patients are infected with genotype 1b HCV, it is known that a small proportion of patients show different results from two typing methods. This study focused on such patients and the effectiveness of treatment with daclatasvir plus asunaprevir (DCV/ ASV) was evaluated. We analyzed 644 DCV/ASV-treated patients with serotype 1 or genotype 1b, and among them, 166 serotype-1 patients received a commercial-based direct sequencing (DS) test for resistant-associated variants of genotype 1b HCV. We found four patients (2.4%) with DS test failure, suggesting that the PCR primers targeting genotype 1b may not match. Importantly, none of the four patients achieved a sustained virological response. Our in-house DS test analyzing the 5′-untranslated region and coding regions for NS4 and NS5B of HCV showed that three of the four patients were infected with genotype 2 HCV, and one patient was infected with genotype 1a HCV. No recombinant virus of different genotypes was found. This study indicates that a subset of serotype-1 hepatitis C patients is infected with HCV of genotype 2 or 1a in Japan and that DCV/ASV is not effective for such patients. Thus, attention should be paid to DAA treatment without HCV genotyping.

Discrepant Diagnostic Results of Nested Polymerase Chain Reaction-based Genotyping in a Patient with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection

“…In Japan, an HCV serotyping assay using non-structural protein 4 (NS 4)-specific antibodies is commonly used (3), as an HCV genotyping assay based on the nested PCR method is not approved for coverage by the national health insurance program. When determining HCV genotypes, the frequency of discrepancy between the serotype and genotype is reported to be low (4,16,17), but some clinically problematic cases have been reported (5)(6)(7). Such discrepancies may be caused by coinfection of different genotypes of HCV (6) or infection with an intergenotypic recombinant virus (7).…”

The Successful Retreatment with Glecaprevir and Pibrentasvir of Genotype 1 or 2 HCV-infected Hemodialysis Patients who Failed to Respond to NS5A and Protease Inhibitor Treatment

“…Inoue et al reported that at least 1.8% (3/168) patients who were treated with daclatasvir and asunaprevir, showed discrepancies in their HCV serotype and genotype examination results. Importantly, all of the three patients failed to respond to daclatasvir and asunaprevir (24). Thus, it is possible that a certain number of patients, for whom only an HCV serotype examination has been conducted (because this is the only examination approved in Japan) and who have failed to respond to daclatasvir and asunaprevir treatment, might have HCV genotype 2 infection.…”