Comparison of test results of serogrouping and core region PCR-based genotyping in patients with chronic hepatitis C virus infection: Analysis of inderminate or discrepant cases and identification of a 2b/1b recombinant HCV

達也, 相川; 文男, 津田; ちさと, 上野; 陽子, 菊池; 浩史, 大西; 勉, 西澤; 宏明, 岡本

doi:10.2957/kanzo.57.447

Cited by 7 publications

(9 citation statements)

References 16 publications

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“…Of note, recombination crossover points were located near the junctional site of NS2 and NS3 regions in all nine isolates showing intergenotypic 2b/1b recombination , from nt 2960/2961 to nt 3169–3171. In the present patient, the crossover point was estimated at nt 3114/3115, which corresponds to the N‐terminal site of the NS3 region, whereas the other three HCV strains reported from Japanese institutes showed a crossover point at nt 2960/2961 . Furthermore, the crossover points of strains reported from the USA, the Philippines, and Puerto Rico differed from each other as well as from the Japanese strains .…”

Section: Discussioncontrasting

confidence: 57%

“…reported that the HCV serotypes are indeterminate in 11.1% of Japanese patients with HCV infection . Moreover, they showed that a discrepancy existed between genotypes and serogroups of HCV in 1.4% of patients in their cohort, and intergenotypic recombinant HCV strains may contribute to such discrepancy . In the present paper, we report a patient with HCV who showed a discrepancy between the genotype (2b) and the serogroup (type 1) because of an intergenotype 2b/1b recombination.…”

Section: Introductionmentioning

confidence: 58%

“…Various types of intergenotypic recombinant HCV strains have been reported worldwide, including intergenotype 2b/1a, 2k/1b, 2i/6p, 2a/1a, 2b/6w, 3a/1b, and 2/5 as well as intergenotype 2b/1b. In Japan, however, intergenotypic 2b/1b recombinant HCV strains have been exclusively reported, as shown in Table . Of note, recombination crossover points were located near the junctional site of NS2 and NS3 regions in all nine isolates showing intergenotypic 2b/1b recombination , from nt 2960/2961 to nt 3169–3171.…”

Section: Discussionmentioning

confidence: 99%

“…Although most patients with genotype 1b HCV and genotypes 2a and 2b HCV are diagnosed as having serogroup 1 HCV and serogroup 2 HCV, respectively, Aikawa et al . reported that the HCV serotypes are indeterminate in 11.1% of Japanese patients with HCV infection . Moreover, they showed that a discrepancy existed between genotypes and serogroups of HCV in 1.4% of patients in their cohort, and intergenotypic recombinant HCV strains may contribute to such discrepancy .…”

Section: Introductionmentioning

confidence: 98%

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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

Kurata

Uchida

Kouyama

et al. 2017

Hepatology Research

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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.

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Section: Discussioncontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

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

Kurata

Uchida

Kouyama

et al. 2017

Hepatology Research

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“…with HCV of genotype 2a or 2b, one patient had mixed infection of genotype 1b and 2a, and one patient had recombinant HCV of genotype 2b and 1b (Aikawa et al 2016). In this study, there were three patients of serotype 1/genotype 2, but no patients had recombinant virus of different genotypes, because the genotypes based on the sequences in 5′ UTR, NS4 region, and NS5B region were consistent.…”

Section: Discussionmentioning

confidence: 85%

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

Inoue

Kanno

Wakui

et al. 2017

Tohoku J. Exp. Med.

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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.

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

Okada

Hoang

Tamori

et al. 2018

Clin J Gastroenterol

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There have been a few reports on the treatment of patients infected with recombinant hepatitis C virus (HCV) genotype 2/1 strains with direct-acting antivirals (DAAs). We experienced three patients, with genotype 2/1 recombinant HCV, treated with DAAs successfully. The first, a 39-year-old man, was infected with recombinant HCV genotype 2a/1b, a rare variant. The sequence of the relapsed virus showed chimeric HCV 2a/1b with the recombinant breakpoint found at nucleotide +49 from the start of the NS3 region. Sofosbuvir plus ribavirin, a regimen recommended for HCV genotype 2, did not lead to a sustained viral response (SVR). Retreatment with grazoprevir plus elbasvir resulted in an SVR. The second case, a 70-year-old woman, was infected with recombinant HCV genotype 2b/1b. DAA therapy with sofosbuvir plus ledipasvir resulted in an SVR. The third case, a 48-year-old woman, was also infected with recombinant HCV genotype 2b/1b. DAA therapy with daclatasvir plus asunaprevir resulted in an SVR. The baseline sequences of the viruses from both the second and third cases showed chimeric HCV 2b/1b with the recombinant breakpoint found at 4 nucleotide +10 from the NS3 start. We report three cases with 2/1 chimeras and discuss the prevalence and response to therapy.

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Comparison of test results of serogrouping and core region PCR-based genotyping in patients with chronic hepatitis C virus infection: Analysis of inderminate or discrepant cases and identification of a 2b/1b recombinant HCV

Cited by 7 publications

References 16 publications

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

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

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

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

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