title: Amino acid substitution in HCV core/NS5A region and genetic variation near IL28B gene affect treatment efficacy to interferon plus ribavirin combination therapy.
abstract: OBJECTIVE
  To evaluate predictive factors of treatment efficacy to interferon (IFN)/ribavirin in patients infected with HCV genotype 1b (HCV-1b).
  
  
  METHODS
  This study investigated pretreatment predictors, including viral- (aa substitutions in core aa 70/91 and NS5A-ISDR/IRRDR) and host-related factors (genetic variation near IL28B gene), to 48-week IFN/ribavirin in 490 Japanese adults infected with HCV-1b.
  
  
  RESULTS
  The proportion of patients who showed end-of-treatment response (ETR), sustained virological response (SVR), and SVR after ETR was 76, 54, and 76%, respectively. There was a significant positive correlation between the number of aa substitutions in ISDR and those in IRRDR. Concerning the substitution of core aa 91, the number of aa substitutions in ISDR/IRRDR of patients with Leu91 was significantly higher than that of patients with Met91. Furthermore, levels of viremia were influenced by aa substitutions in core aa 91 and ISDR/IRRDR. By multivariate analysis, rs8099917 genotype was an important predictor of ETR and SVR. With regard to viral factors, core aa 70/91 was an important predictor of ETR, and SVR after ETR. ISDR was an important predictor of SVR, and SVR after ETR.
  
  
  CONCLUSIONS
  aa substitution in core/NS5A region and genetic variation near IL28B were important predictors of treatment efficacy to IFN/ribavirin.
authors: Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp
authors: Norio
authors: N
authors: Akuta
authors: Fumitaka
authors: F
authors: Suzuki
authors: Miharu
authors: M
authors: Hirakawa
authors: Yusuke
authors: Y
authors: Kawamura
authors: Hitomi
authors: H
authors: Sezaki
authors: Yoshiyuki
authors: Y
authors: Suzuki
authors: Tetsuya
authors: T
authors: Hosaka
authors: Masahiro
authors: M
authors: Kobayashi
authors: Mariko
authors: M
authors: Kobayashi
authors: Satoshi
authors: S
authors: Saitoh
authors: Yasuji
authors: Y
authors: Arase
authors: Kenji
authors: K
authors: Ikeda
authors: Kazuaki
authors: K
authors: Chayama
authors: Yusuke
authors: Y
authors: Nakamura
authors: Hiromitsu
authors: H
authors: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D014644:Genetic Variation; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D000095022:Interferon Lambda; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C069130:nucleocapsid protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase