title: Correlation between polymorphism in the inosine triphosphatase and the reductions in hemoglobin concentration and ribavirin dose during sofosbuvir and ribavirin therapy.
abstract: OBJECTIVE
  It is unclear whether polymorphism in the inosine triphosphatase (ITPA) gene correlates to the reduction in hemoglobin (Hb) concentrations during sofosbuvir (SOF) and ribavirin (RBV) therapy. This study investigated the effects of the ITPA polymorphism on Japanese patients with chronic hepatitis C virus genotype 2 infection treated with SOF/RBV therapy.
  
  
  METHODS
  In 106 patients treated with SOF/RBV therapy, this study assessed the effects of the ITPA polymorphism (rs1127354) on anemia, RBV dose reduction, and sustained virological response.
  
  
  RESULTS
  Of the 106 patients, 80 had the CC genotype, whereas 26 had a non-CC genotype in ITPA. Patients with the CC genotype had significantly larger reductions in Hb concentrations than those with a non-CC genotype throughout the treatment course. RBV dose reduction was required in 18/106 (17.0%) patients, with a significantly higher frequency in patients with the CC genotype than in those with a non-CC genotype (P = 0.010). In multivariate analysis, age ≥ 65 years (P = 0.011) and the ITPA CC genotype (P < 0.0001) were factors significantly associated with anemia throughout the treatment course. Sustained virological response was achieved in 99.0% of all patients: 98.7% of patients with the CC genotype and 100% of patients with a non-CC genotype.
  
  
  CONCLUSIONS
  Inosine triphosphatase polymorphism appeared to correlate with anemia incidence and RBV dose reduction during SOF/RBV therapy, but not the clinical outcome. Careful monitoring of Hb concentrations and prompt adjustment of RBV doses are required for successful treatment, particularly in patients harboring the ITPA CC genotype or age ≥ 65 years.
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Ritsuzo
authors.initials: R
authors.lastname: Kozuka
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hoang
authors.initials: H
authors.lastname: Hai
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yuga
authors.initials: Y
authors.lastname: Teranishi
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Motoyama
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kawamura
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hagihara
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Uchida-Kobayashi
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Morikawa
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Enomoto
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000743:Anemia, Hemolytic / Q000139:chemically induced; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011755:Pyrophosphatases / Q000235:genetics*; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage* / Q000009:adverse effects; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D011755:Pyrophosphatases; D012254:Ribavirin; D000069474:Sofosbuvir; D000097630:Inosine Triphosphatase
keywords: hemolytic anemia; hepatitis C virus; inosine triphosphatase; single-nucleotide polymorphism; sustained virological response