title: Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy.
abstract: OBJECTIVE
  A proportion of patients infected with genotype 2a hepatitis C virus (HCV) cannot achieve a sustained virological response (SVR) to pegylated-interferon plus ribavirin therapy (PEG-IFN/RBV) but the reason remains unclear. The present study aimed to clarify the possible correlation between viral sequence variations and final outcome.
  
  
  METHODS
  The pretreatment complete open reading frame (ORF) sequences of genotype 2a HCV were determined by direct sequencing for two independent groups of patients (43 patients as test; group 1 and 35 as validation; group 2), and the correlation with the final outcome was explored.
  
  
  RESULTS
  Patients with SVR (n = 58) and with non-SVR (n = 20) differed significantly in pretreatment HCV RNA level (p = 0.002), fibrosis score (p = 0.047), and cumulative RBV dosage (p = 0.003). By comparison of all amino acid positions in the complete HCV ORFs, threonine at amino acid (aa) 110 in the core region was remarkably frequent in SVR (p = 0.01 for group 1, p = 0.004 for group 2, and p = 5E-05 for combined). A sliding window analysis revealed that the total number of amino acid variations within the NS5A aa 2258-2306 region were significantly high in SVR compared to non-SVR patients (p = 0.01 for group 1, p = 0.006 for group 2, and p = 0.0006 for combined). Multivariate analyses revealed that core aa 110 (p = 0.02), NS5A aa 2258-2306 (p = 0.03), and cumulative RBV dosage (p = 0.02) were identified as independent variables associated with the final outcome.
  
  
  CONCLUSIONS
  The outcome of PEG-IFN/RBV therapy is significantly influenced by variation in the core and NS5A regions in genotype 2a HCV infection.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, 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