title: ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin.
abstract: OBJECTIVE
  Sofosbuvir (SOF) and ribavirin (RBV) combination therapy produces a sustained response in many patients with genotype 2 chronic hepatitis C. However, RBV-induced anemia is a troublesome side-effect that may limit this treatment. Genetic variation leading to inosine triphosphatase (ITPA) deficiency is known to protect against RBV-induced hemolytic anemia. This study aimed to evaluate the relationships between the efficacy and safety of SOF/RBV treatment and ITPA gene variants.
  
  
  METHODS
  Ninety patients with genotype 2 chronic hepatitis C treated with SOF/RBV were studied. The relationships among genetic polymorphisms of ITPA and the decline in hemoglobin levels from baseline, RBV dose reduction, and sustained virological response (SVR) rates were analyzed.
  
  
  RESULTS
  Overall SVR at 12 weeks was 94.4% (85/90). Patients with the ITPA CA/AA genotypes had a lower degree of anemia throughout the therapy than those with the ITPA CC genotype. The percentage of patients requiring RBV dose reduction was significantly lower for those with the ITPA CA/AA variation, a difference even more apparent when the pretreatment hemoglobin level was <12 g/dL. The dose reduction of RBV and serum albumin level were significantly associated with SVR.
  
  
  CONCLUSIONS
  Patients with the ITPA CA/AA genotype were less likely to develop anemia than those with the ITPA CC genotype and were more likely to complete SOF/RBV therapy. These results may provide a valuable pharmacogenetic diagnostic tool to predict drug-induced adverse events, particularly in patients with pre-existing anemia.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Clinical Laboratory, Medical Hospital of Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Miyako
authors.identifier: http://orcid.org/0000-0002-0468-4409
authors.initials: M
authors.lastname: Murakawa
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.|Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Asahina
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagata
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.|Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Kakinuma
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Nitta
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Fukiko
authors.initials: F
authors.lastname: Kawai-Kitahata
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Otani
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Miyoshi
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Asano
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Itsui
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Seishin
authors.initials: S
authors.lastname: Azuma
authors.affiliation: Showa General Hospital, Tokyo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nouchi
authors.affiliation: Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Furumoto
authors.affiliation: Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Asano
authors.affiliation: Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Chuganji
authors.affiliation: Department of Clinical Laboratory, Medical Hospital of Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Tohda
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
keywords: anemia; hepatitis C virus; inosine triphosphatase; single nucleotide polymorphism