Chronic hepatitis caused by hepatitis C virus showing a discrepancy between serogroup and genotype because of intergenotypic 2b/1b recombination: A pitfall in antiviral therapy with direct‐acting antivirals

Abstract

A 40-year-old male patient with virologic relapse after daclatasvir plus asunaprevir therapy for a serogroup 1 hepatitis C virus (HCV) infection visited our hospital for retreatment. Virologic examinations revealed that a genotype 2b HCV strain carrying both NS3-S122N / D168A and NA5A-R30Q / L31M / Q54H / Y93H mutations had relapsed. The patient received sofosbuvir plus ribavirin therapy, but virologic relapse occurred once again. Sequencing of the HCV genome clarified an intergenotypic recombination of 2b and 1b with an estimated crossover point between nucleotides 3114 and 3115, corresponding to the N-terminal end of the NS3 region (DDBJ/EMBL/GenBank databases accession no. LC273304). The NS5B-S282T mutation was not detected in the HCV strain, and resistance-association substitutions in the NS3 and NS5A regions were similar to those at baseline. Direct sequencing of the core and NS4A regions corresponding to the targeting sites of genotyping and serogrouping, respectively, is useful to determine the combination of direct-acting antivirals when a discrepancy is observed between the serogroup and genotype of HCV strains.

Successful direct-acting antiviral treatment of three patients with genotype 2/1 recombinant hepatitis C virus

“…The original 2k/1b chimera is prevalent (14~25%) in Russia, Georgia, Germany, and Israel [3,9,10]. In comparison, the original 2b/1a chimeric HCV was predominant in Western Europe and North America [10,12], while the original 2b/1b chimera was identified in Japan and the Philippines [13,14]. The first 2a/1b chimeric HCV variant originated from Russia [3], and our case was the second report of 2a/1b recombinant HCV.…”

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).…”

“…Several methods for HCV typing are clinically available, but only serotyping (3), not genotyping, is approved for coverage by the public health insurance program in Japan. The serotyping method can distinguish type 1 (group 1) and type 2 (group 2) with high accuracy (4), but there are a few dis-crepancies between serotypes and genotypes in some patients that can lead to treatment failure (5)(6)(7).…”

A case of genotype‐3b hepatitis C virus in which the whole genome was successfully analyzed using third‐generation nanopore sequencing

“…In the MinION nanopore sequencer analysis, random primers consisting of nine nucleotides (262 144 types) were used for the amplification, similar to second‐generation deep sequencing, suggesting that almost the whole genome of any genotype/subgenotype strain can be amplified and subjected to nucleotide sequencing. Previously, we had reported intergenotypic 2b/1b recombinant HCV strains in a patient manifesting discrepancy between serogroup and genotype . In such patients, the MinION nanopore sequencer could be useful to identify recombination breakpoints, as this method does not require the design of genotype‐specific primers.…”

“…Previously, we had reported intergenotypic 2b/1b recombinant HCV strains in a patient manifesting discrepancy between serogroup and genotype. 22 In such patients, the MinION nanopore sequencer could be useful to identify recombination breakpoints, as this method does not require the design of genotype-specific primers. Furthermore, the full-length sequencing for intergenotypic recombination HCV strains could be achieved successfully using the MinION nanopore sequencer.…”