title: Analysis of the complete open reading frame of genotype 2b hepatitis C virus in association with the response to peginterferon and ribavirin therapy.
abstract: OBJECTIVE
  Patients infected with genotype 2b hepatitis C virus (HCV) generally can achieve favorable responses to pegylated-interferon plus ribavirin therapy (PEG-IFN/RBV). However, a proportion of patients show poorer responses and the correlation between viral sequence variation and treatment outcome remains unclear.
  
  
  METHODS
  The pretreatment complete open reading frame (ORF) sequences of genotype 2b HCV determined by direct sequencing were investigated for correlation with the final outcome in a total of 60 patients.
  
  
  RESULTS
  In this study group, 87.5% (14/16) of non-sustained virological response (non-SVR) patients (n = 16) were relapsers. Compared to sustained virological response (SVR) patients (n = 44), non-SVR patients were older and could not achieve prompt viral clearance after the therapy induction. Comparing each viral protein between the two groups, viral sequences were more diverse in SVR patients and that diversity was found primarily in the E1, p7, and NS5A proteins. In searching for specific viral regions associated with the final outcome, several regions in E2, p7, NS2, NS5A, and NS5B were extracted. Among these regions, part of the interferon sensitivity determining region (ISDR) was included. In these regions, amino acid substitutions were associated with the final outcome in an incremental manner, depending upon the number of substitutions.
  
  
  CONCLUSIONS
  Viral sequences are more diverse in SVR patients than non-SVR patients receiving PEG-IFN/RBV therapy for genotype-2b HCV infection. Through systematic comparison of viral sequences, several specific regions, including part of the ISDR, were extracted as having significant correlation with the final outcome.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kadokura
authors.forename: Shinya
authors.initials: S
authors.lastname: Maekawa
authors.forename: Ryota
authors.initials: R
authors.lastname: Sueki
authors.forename: Mika
authors.initials: M
authors.lastname: Miura
authors.forename: Kazuki
authors.initials: K
authors.lastname: Komase
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shindo
authors.forename: Fumitake
authors.initials: F
authors.lastname: Amemiya
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Uetake
authors.forename: Taisuke
authors.initials: T
authors.lastname: Inoue
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016366:Open Reading Frames / Q000235:genetics*; D010802:Phylogeny; D012254:Ribavirin / Q000494:pharmacology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D014764:Viral Proteins; D012254:Ribavirin