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ITPA gene variation and ribavirin‐induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin
Author(s) -
Murakawa Miyako,
Asahina Yasuhiro,
Nagata Hiroko,
Nakagawa Mina,
Kakinuma Sei,
Nitta Sayuri,
KawaiKitahata Fukiko,
Otani Satoshi,
Kaneko Shun,
Miyoshi Masato,
Tsunoda Tomoyuki,
Asano Yu,
Sato Ayako,
Itsui Yasuhiro,
Azuma Seishin,
Nouchi Toshihiko,
Furumoto Yohei,
Asano Tooru,
Chuganji Yoshimichi,
Tohda Shuji,
Watanabe Mamoru
Publication year - 2017
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12867
Subject(s) - itpa , ribavirin , medicine , anemia , gastroenterology , sofosbuvir , genotype , hemolytic anemia , hepatitis c , hepatitis c virus , immunology , biology , genetics , gene , virus
Aim 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.