title: IL28B but not ITPA polymorphism is predictive of response to pegylated interferon, ribavirin, and telaprevir triple therapy in patients with genotype 1 hepatitis C.
abstract: BACKGROUND
  Pegylated interferon, ribavirin, and telaprevir triple therapy is a new strategy expected to eradicate the hepatitis C virus (HCV) even in patients infected with difficult-to-treat genotype 1 strains, although adverse effects, such as anemia and rash, are frequent.
  
  
  METHODS
  We assessed efficacy and predictive factors for sustained virological response (SVR) for triple therapy in 94 Japanese patients with HCV genotype 1. We included recently identified predictive factors, such as IL28B and ITPA polymorphism, and substitutions in the HCV core and NS5A proteins.
  
  
  RESULTS
  Patients treated with triple therapy achieved comparatively high SVR rates (73%), especially among treatment-naive patients (80%). Of note, however, patients who experienced relapse during prior pegylated interferon plus ribavirin combination therapy were highly likely to achieve SVR while receiving triple therapy (93%); conversely, prior nonresponders were much less likely to respond to triple therapy (32%). In addition to prior treatment response, IL28B SNP genotype and rapid viral response were significant independent predictors for SVR. Patients with the anemia-susceptible ITPA SNP rs1127354 genotype typically required ribavirin dose reduction earlier than did patients with other genotypes.
  
  
  CONCLUSIONS
  Analysis of predictive factors identified IL28B SNP, rapid viral response, and transient response to previous therapy as significant independent predictors of SVR after triple therapy.
authors.affiliation: Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Japan. chayama@hiroshima-u.ac.jp
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Karino
authors.forename: Joji
authors.initials: J
authors.lastname: Toyota
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage* / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011755:Pyrophosphatases / Q000235:genetics*; D012254:Ribavirin / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D000095022:Interferon Lambda; D012324:RNA-Dependent RNA Polymerase; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D011755:Pyrophosphatases; D012254:Ribavirin; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C069130:nucleocapsid protein, Hepatitis C virus; C486464:telaprevir; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase