title: Amino acid substitution in HCV core region and genetic variation near the IL28B gene affect viral dynamics during telaprevir, peginterferon and ribavirin treatment.
abstract: OBJECTIVE
  Genetic variation near the IL28B gene and substitution of aa 70 and 91 in the core region of HCV-1b are useful as predictors of treatment efficacy to telaprevir/pegylated interferon (PEG-IFN)/ribavirin, but its impact on viral dynamics is not clear.
  
  
  METHODS
  This study investigated predictive factors of viral dynamics during 12- or 24-week regimen of triple therapy in 80 Japanese adults infected with HCV-1b.
  
  
  RESULTS
  After 24 h of commencement of treatment, the proportion of patients with Arg70 and Leu91 substitutions in the core region who showed ≥3.0 log drop in HCV RNA level was significantly higher than that of patients with Gln70 (His70) and/or Met91. At 8 and 12 weeks, HCV RNA loss rate of patients with rs8099917 genotype TT near IL28B gene was significantly higher than that of patients with non-TT. Multivariate analysis identified substitution of aa 70 and 91 as a predictor of ≥3.0 log fall in HCV RNA level at 24 h (Arg70 and Leu91) and SVR (Arg70), and rs8099917 (TT) as a predictor of HCV RNA loss at 12 weeks and SVR.
  
  
  CONCLUSIONS
  This study identified genetic variation near IL28B gene and aa substitution of the core region as predictors of viral dynamics during triple therapy.
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Miharu
authors.initials: M
authors.lastname: Hirakawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yatsuji
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D014758:Viral Core Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C486464:telaprevir; C417083:peginterferon alfa-2b