title: IFNL4 polymorphism effects on outcome of simeprevir, peginterferon, and ribavirin therapy for older patients with genotype 1 chronic hepatitis C.
abstract: OBJECTIVE
  Older patients with chronic hepatitis C have a lower virological response to interferon (IFN)-based treatments compared to younger patients. A single nucleotide polymorphism in the IFN-λ-4 (IFNL4) gene has a potent predictive effect on treatment response to IFN-based treatments. The efficacy of simeprevir (SMV) plus pegylated-IFN (PEG-IFN) and ribavirin therapy and the predictive value of IFNL4 on the outcome of therapy for older patients have not been addressed.
  
  
  METHODS
  This retrospective multicenter study included 234 consecutive Japanese patients with genotype 1 chronic hepatitis C. We assessed the predictive factors for sustained virological response (SVR) to SMV, PEG-IFN, and ribavirin triple therapy in 170 younger (<70 years) and 64 older (≥70 years) patients. IFNL4 polymorphism ss469415590 was analyzed by Invader assay.
  
  
  RESULTS
  The SVR rate for older patients was similar to that for younger patients (63.9% and 72.0%, respectively). The SVR rate for the IFNL4 TT/TT group was significantly higher than the IFNL4 TT/ΔG or ΔG/ΔG group both in younger (93.6% and 46.1%, respectively, P < 0.01) and older patients (84.4% and 33.3%, respectively, P < 0.001). In multivariate regression analysis, IFNL4 TT/TT genotype, response to previous treatment and IFNL4 TT/TT genotype were identified as independent predictive factors for SVR in older and younger patients, respectively. Decrease in hemoglobin level was similar between the two groups.
  
  
  CONCLUSIONS
  The virological response to SMV triple therapy in older patients was similar to that of younger patients. Analysis of IFNL4 polymorphisms is a valuable predictor in both younger and older patients.
authors.affiliation: Department of Gastroenterology/Liver Center, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Mori
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Yoshiiku
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nagaoki
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kawaoka
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hiramatsu
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aikata
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.|Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.|Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Department of Gastroenterology/Liver Center, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors.forename: Yohji
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology/Liver Center, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Takaki
authors.affiliation: Department of Gastroenterology/Liver Center, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tsuji
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.|Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
keywords: IFNL4; chronic hepatitis C; older patient; ribavirin; simeprevir