Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy.

Tatsuya Fujino, Yoko Aoyagi, Mariko Takahashi, Ryoko Yada, Naoko Yamamoto, Yuki Ohishi, Akihiko Nishiura, Motoyuki Kohjima, Tsuyoshi Yoshimoto, Kunitaka Fukuizumi, Manabu Nakashima, Masaki Kato, Kazuhiro Kotoh, Makoto Nakamuta, Munechika Enjoji

Research output: Contribution to journalArticle

Abstract

AIM: To analyzed the association between inosine triphosphatase (ITPA) (rs1127354) genotypes and sustained virological response (SVR) rates in peginterferon (Peg-IFN)α + ribavirin (RBV) treatment. METHODS: Patients who underwent Peg-IFNα + RBV combination therapy were enrolled (n = 120) and they had no history of other IFN-based treatments. Variation in hemoglobin levels during therapy, cumulative reduction of RBV dose, frequency of treatment withdrawal, and SVR rates were investigated in each ITPA genotype. RESULTS: In patients with ITPA CC genotype, hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA genotype. However, SVR rates were equivalent between CC and CA/AA genotypes, and within a subset of patients with Interleukin 28B (IL28B) (rs8099917) TT genotype, SVR rates tended to be higher in patients with ITPA CC genotype, although the difference was not significant. CONCLUSION: ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV dose. However, CC genotype was not inferior to CA/AA genotype for SVR rates. When full-length treatment is accomplished, it is plausible that more SVR is achieved in patients with ITPA CC variant, especially in a background of IL28B TT genotype.
Original languageEnglish
Pages (from-to)54-60
Number of pages7
JournalWorld journal of gastrointestinal pharmacology and therapeutics
Volume4
Issue number3
DOIs
Publication statusPublished - Aug 6 2013

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