title: Mutations in the core and NS5A region of hepatitis C virus genotype 1b and correlation with response to pegylated-interferon-alpha 2b and ribavirin combination therapy.
abstract: Mutations in two regions of hepatitis C virus (HCV) have been implicated in influencing response to interferon (IFN) therapy. Substitutions in the NS5A region of HCV have been associated with response to IFN therapy, and this region has been known as the IFN sensitivity-determining region (ISDR). The mutations in the core region of HCV have also been reported to predict IFN response. The aim of this study was to investigate whether amino acid substitutions in the core region and ISDR among patients with HCV genotype 1b affect the response to IFN therapy. A total of 213 patients who completed IFN treatment were randomly selected. All patients received pegylated-IFN-alpha 2b once each week, plus oral ribavirin daily for 48 weeks. Of the 213 patients, 117 (54.9%) showed early virologic response (EVR), with HCV-negativity, at 12 weeks. Factors related to EVR on multivariate analysis were non-Gln70 and Leu91 in the core region, and ISDR mutant-type. One hundred and two (47.9%) showed a sustained virologic response (SVR). SVR occurred more frequently in patients without Gln70 (55.4%) than in those with Gln70 (21.3%) (P < 0.0001). SVR was achieved in 43.6% of patients with wild-type ISDR and 62.5% of patients with mutant-type (P = 0.0227). Of the 34 patients who simultaneously had non-Gln70 and mutant-type ISDR, 26 (76.5%) achieved SVR. Factors related to SVR on multivariate analysis were non-Gln70 and ISDR mutant-type. In conclusion, amino acid substitutions in the core region and ISDR were useful for predicting the response to IFN in patients with HCV genotype 1b.
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Tsuruma-cho, Showa-ku, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Katano
authors.forename: M
authors.initials: M
authors.lastname: Ishigami
authors.forename: A
authors.initials: A
authors.lastname: Itoh
authors.forename: Y
authors.initials: Y
authors.lastname: Hirooka
authors.forename: I
authors.initials: I
authors.lastname: Nakano
authors.forename: F
authors.initials: F
authors.lastname: Urano
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
authors.forename: H
authors.initials: H
authors.lastname: Toyoda
authors.forename: T
authors.initials: T
authors.lastname: Kumada
authors.forename: H
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011379:Prognosis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C417083:peginterferon alfa-2b