title: Predictive value of the IFNL4 polymorphism on outcome of telaprevir, peginterferon, and ribavirin therapy for older patients with genotype 1b chronic hepatitis C.
abstract: BACKGROUND
  Older patients with chronic hepatitis C have a lower virological response to interferon (IFN) treatment compared to younger patients. The efficacy of telaprevir (TVR) and PEG-IFN plus ribavirin combination therapy and the predictive value of recently identified IFN lambda (IFNL) 4 polymorphisms on the outcome of therapy for older patients have not been addressed.
  
  
  METHODS
  We assessed predictive factors for sustained virological response (SVR) to triple therapy in 226 younger (≤65 years) and 87 older (>65 years) Japanese patients with chronic genotype 1 hepatitis C. IFNL4 polymorphism ss469415590 was analyzed by Invader assay.
  
  
  RESULTS
  The SVR rate for older patients was slightly lower than for younger patients (69 vs. 82%, P = 0.043). In the older group, the SVR rate for patients with the IFNL4 TT/TT genotype was significantly higher than patients with TT/ΔG or ΔG/ΔG genotypes (81.8 and 42.9%, P = 0.003). In multivariate regression analysis, rapid virological response (OR 36.601, P = 0.002) and IFNL4 TT/TT genotype (OR 19.502, P = 0.009) were identified as significant independent predictors for SVR in older patients. Treatment-related decreases in hemoglobin and increases in serum creatinine were higher in older patients than younger patients. Reduction of initial TVR dose to 1,500 mg per day alleviated these adverse events without compromising SVR rate in older patients.
  
  
  CONCLUSIONS
  Analysis of IFNL4 polymorphisms is a valuable predictor in older patients receiving TVR triple therapy. 1,500 mg per day is a suitable initial TVR dose for older Japanese patients.
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Hatsue
authors.initials: H
authors.lastname: Fujino
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nagaoki
authors.forename: Yoshiiku
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kan
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Masaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ono
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahara
authors.forename: Youji
authors.initials: Y
authors.lastname: Honda
authors.forename: Noriaki
authors.initials: N
authors.lastname: Naeshiro
authors.forename: Ayako
authors.initials: A
authors.lastname: Urabe
authors.forename: Satoe
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miyaki
authors.forename: Eisuke
authors.initials: E
authors.lastname: Murakami
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kawaoka
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.forename: Akira
authors.initials: A
authors.lastname: Hiramatsu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aikata
authors.forename: Shoichi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.forename: Waka
authors.initials: W
authors.lastname: Ohishi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012044:Regression Analysis; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007378:Interleukins; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C579163:IFNL4 protein, human; D000095022:Interferon Lambda; C486464:telaprevir; C417083:peginterferon alfa-2b