title: Effects of ITPA polymorphism on decrease of hemoglobin during simeprevir, peg-interferon, and ribavirin combination treatment for chronic hepatitis C.
abstract: OBJECTIVE
  Polymorphisms in the ITPA gene influence anemia during peg-interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with simeprevir, PEG-IFN, and RBV are not sufficiently known.
  
  
  METHODS
  We analyzed 212 patients with genotype 1 chronic hepatitis C, who were treated with simeprevir plus PEG-IFN/RBV triple therapy, and assessed the effect of the ITPA polymorphism on hemoglobin levels and RBV dose reduction. ITPA (rs1127354) and IFNL4 (ss469415590) polymorphisms were genotyped using the Invader assay. A stepwise multivariate regression analysis was carried out to identify factors associated with outcome of the therapy.
  
  
  RESULTS
  Reduction of hemoglobin levels was similar between patients treated with simeprevir plus PEG-IFN/RBV and those treated with PEG-IFN/RBV therapy. In simeprevir plus PEG-IFN/RBV-treated patients, decreases in hemoglobin levels were faster and greater, and the cumulative proportion of patients with ribavirin dose reduction was significantly greater in ITPA genotype CC patients than in CA/AA patients. The total dose of simeprevir and PEG-IFN was similar between ITPA genotype CC and CA/AA patients. In contrast, the total dose of RBV was lower in patients with the CC genotype. Multivariate analysis showed that the IFNL4 TT/TT genotype, but not the ITPA SNP genotype, treatment history (treatment-naive or relapse during prior treatment), and treatment completion were significantly associated with outcome of therapy.
  
  
  CONCLUSIONS
  ITPA polymorphism influences hemoglobin levels and incidence of RVB dose reduction during simeprevir triple therapy, indicating the importance of monitoring anemia during treatment, particularly for ITPA genotype CC patients.
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Morio
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, 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 Sciences, 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 Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Reona
authors.initials: R
authors.lastname: Morio
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hatooka
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kan
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hatsue
authors.initials: H
authors.lastname: Fujino
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukuhara
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Masaki
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ono
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahara
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Urabe
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Satoe
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, 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 Sciences, 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 Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, 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 Sciences, 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 Sciences, 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 Sciences, 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 Sciences, 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 and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, 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: ITPA; chronic hepatitis C; hemoglobin; ribavirin; simeprevir