title: 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.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine.
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kanno
authors.forename: Yuta
authors.initials: Y
authors.lastname: Wakui
authors.forename: Masahito
authors.initials: M
authors.lastname: Miura
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Morosawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kogure
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakazu
authors.forename: Masashi
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujisaka
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Umetsu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takai
authors.forename: Takuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002219:Carbamates; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D011759:Pyrrolidines; D012703:Serotyping; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir; C571889:asunaprevir