title: Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: a Japanese multi-center study.
abstract: BACKGROUND
  Chronic hepatitis C (CHC) genotype 1b patients with high viral load are resistant to peginterferon (PEG-IFN) and ribavirin (RBV) combination therapy, especially older and female patients.
  
  
  METHODS
  To elucidate the factors affecting early and sustained viral responses (EVR and SVR), 409 genotype 1b patients CHC with high viral loads who had received 48 weeks of PEG-IFN/RBV therapy were enrolled. The amino acid (aa) sequences of the HCV core at positions 70 and 91 and of the interferon sensitivity determining region (ISDR) were analyzed. Host factors, viral factors, and treatment-related factors were subjected to multivariate analysis.
  
  
  RESULTS
  Male gender, low HCV RNA load, high platelet count, two or more aa mutations of ISDR, and wild type of core aa 70 were independent predictive factors for SVR. In patients with over 80% adherences to both PEG-IFN and RBV, male gender, mild fibrosis stage, and wild type of core aa 70 were independent predictors for SVR.
  
  
  CONCLUSIONS
  Independent predictive factors for SVR were: no aa substitution at core aa 70, two or more aa mutations in the ISDR, low viral load, high values of platelet count, mild liver fibrosis and male gender.
authors.affiliation: Hepatology Center, Saiseikai Suita Hospital, 1-2 Kawazonocho, Suita, 564-0013, Japan. okanoue@suita.saiseikai.or.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Kohichiroh
authors.initials: K
authors.lastname: Yasui
authors.forename: Masahito
authors.initials: M
authors.lastname: Minami
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Morikazu
authors.initials: M
authors.lastname: Onji
authors.forename: Joji
authors.initials: J
authors.lastname: Toyota
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D007564:Japan; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011092:Polyethylene Glycols / Q000494:pharmacology; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology; D012307:Risk Factors; D012737:Sex Factors; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D055815:Young Adult; 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; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C417083:peginterferon alfa-2b