title: Mutations in the interferon sensitivity-determining region of hepatitis C virus genotype 2a correlate with response to pegylated-interferon-alpha 2a monotherapy.
abstract: The interferon sensitivity-determining region (ISDR) is thought to be inhibited by the double-stranded RNA-dependent protein kinase (PKR). Several studies have reported a relationship between the ISDR and interferon (IFN) responsiveness. However, this relationship is controversial. The aim of this study was to investigate whether genomic heterogeneity of the ISDR among patients with hepatitis C virus (HCV) genotype 2a affects the response to pegylated-IFN-alpha 2a monotherapy. Eighty patients (47 men, 33 women; mean age: 54.2 +/- 12.9 years) infected with HCV genotype 2a were evaluated. HCV viral loads were determined by real-time PCR. The ISDR (amino acids 2193-2228) was examined by direct sequencing. Thirty-one patients received subcutaneous injections of pegylated-IFN-alpha 2a (180 microg) once weekly for 24 weeks, and 35 patients received injections for 48 weeks. Fourteen patients withdrew from treatment. Of the remaining 66 patients, 51 (77.3%) showed a sustained virologic response. Factors related to sustained virologic response on multivariate analysis were rapid virologic response (negative HCV at 4 weeks; odds ratio: 0.033; 95% confidence interval (95% CI) 0.003-0.363; P = 0.0052) and the number of mutations in the ISDR (odds ratio: 0.025; 95% CI 0.001-0.476; P = 0.0141). There were no significant differences in other factors, including sex, age, aspartate aminotransferase, alanine aminotransferase, platelet count, duration of treatment, and HCV viral load. Rapid virologic response and the ISDR sequence variations are significantly associated with response to pegylated-IFN-alpha 2a monotherapy in Japanese patients with HCV genotype 2a.
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Katano
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Itoh
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Isao
authors.initials: I
authors.lastname: Nakano
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Urano
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a