PURPOSE: 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.
PURPOSE: 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: K Chayama; F Suzuki; A Tsubota; M Kobayashi; Y Arase; S Saitoh; Y Suzuki; N Murashima; K Ikeda; N Takahashi; M Kinoshita; H Kumada Journal: Hepatology Date: 2000-11 Impact factor: 17.425
Authors: A M Di Bisceglie; P Martin; C Kassianides; M Lisker-Melman; L Murray; J Waggoner; Z Goodman; S M Banks; J H Hoofnagle Journal: N Engl J Med Date: 1989-11-30 Impact factor: 91.245
Authors: M P Manns; J G McHutchison; S C Gordon; V K Rustgi; M Shiffman; R Reindollar; Z D Goodman; K Koury; M Ling; J K Albrecht Journal: Lancet Date: 2001-09-22 Impact factor: 79.321
Authors: Stephanos J Hadziyannis; Hoel Sette; Timothy R Morgan; Vijayan Balan; Moises Diago; Patrick Marcellin; Giuliano Ramadori; Henry Bodenheimer; David Bernstein; Mario Rizzetto; Stefan Zeuzem; Paul J Pockros; Amy Lin; Andrew M Ackrill Journal: Ann Intern Med Date: 2004-03-02 Impact factor: 25.391
Authors: N Enomoto; I Sakuma; Y Asahina; M Kurosaki; T Murakami; C Yamamoto; Y Ogura; N Izumi; F Marumo; C Sato Journal: N Engl J Med Date: 1996-01-11 Impact factor: 91.245
Authors: N Hiramatsu; T Oze; T Yakushijin; Y Inoue; T Igura; K Mochizuki; K Imanaka; A Kaneko; M Oshita; H Hagiwara; E Mita; T Nagase; T Ito; Y Inui; T Hijioka; K Katayama; S Tamura; H Yoshihara; Y Imai; M Kato; Y Yoshida; T Tatsumi; K Ohkawa; S Kiso; T Kanto; A Kasahara; T Takehara; N Hayashi Journal: J Viral Hepat Date: 2009-06-22 Impact factor: 3.728