Brief Article
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World J Gastrointest Pharmacol Ther. Aug 6, 2013; 4(3): 54-60
Published online Aug 6, 2013. doi: 10.4292/wjgpt.v4.i3.54
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
Tatsuya Fujino, Laboratory for Clinical Investigation, National Hospital Organization Nagasaki Medical Center, Ohmura, Nagasaki 856-8562, Japan
Yoko Aoyagi, Ryoko Yada, Naoko Yamamoto, Yuki Ohishi, Akihiko Nishiura, Motoyuki Kohjima, Tsuyoshi Yoshimoto, Kunitaka Fukuizumi, Makoto Nakamuta, Munechika Enjoji, MarikoTakahashi, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka 814-0180, Japan
Manabu Nakashima, Munechika Enjoji, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan
Masaki Kato, Kazuhiro Kotoh, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 814-0180, Japan
Author contributions: Fujino T, Nakamuta M and Enjoji M designed the research; Fujino T, Kohjima M, Yoshimoto T, Fukuizumi K, Kato M and Kotoh K performed the research; Fujino T, Aoyagi Y, Takahashi M, Yada R, Yamamoto N, Ohishi Y and Nishiura A analyzed the data; Fujino T and Enjoji M wrote the paper; Nakashima M and Nakamuta M reviewed it.
Supported by The Research Program of Intractable Disease provided by the Ministry of Health, Labor and Welfare of Japan, and a Grant-in-Aid for Clinical Research from the National Hospital Organization of Japan
Correspondence to: Munechika Enjoji, MD, PhD, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. enjoji@adm.fukuoka-u.ac.jp
Telephone: +81-92-8716631 Fax: +81-92-8630389
Received: March 1, 2013
Revised: May 16, 2013
Accepted: May 18, 2013
Published online: August 6, 2013
Processing time: 152 Days and 23.4 Hours
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.

Keywords: Chronic hepatitis C; Interleukin 28B; Inosine triphosphatase; Peginterferon; Ribavirin

Core tip: Inosine triphosphatase (ITPA) polymorphism at rs1127354 is significantly associated with hemoglobin decline and reduction of ribavirin (RBV) during peginterferon-α + RBV therapy. However, the effect of the ITPA gene single-nucleotide polymorphism on treatment outcome is still unclear. In this study, ITPA CC genotype (rs1127354) was not inferior to CA/AA genotype for sustained virological response rates although CC genotype was a disadvantageous factor for the treatment in relation to completion rates and RBV dose. When full-length treatment is accomplished, the SVR rate tended to be higher in patients with the CC genotype, especially in a subset of patients with the favorable TT genotype (rs8099917) of Interleukin 28B.