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Roles of ITPA and IL28B Genotypes in Chronic Hepatitis C Patients Treated with Peginterferon Plus Ribavirin
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan
Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan
* Author to whom correspondence should be addressed.
Received: 12 June 2012; in revised form: 27 July 2012 / Accepted: 6 August 2012 / Published: 14 August 2012
Abstract: It has been reported that inosine triphosphatase (ITPA) gene variants protect against ribavirin-induced anemia in patients treated for chronic hepatitis C. IL28B variants also influence the treatment response of peginterferon plus ribavirin treatment in these patients. In the present study, we examined how ITPA and IL28B genotypes have clinical impacts on treatment-induced hematotoxicities and treatment response in HCV-infected patients treated with peginterferon plus ribavirin. ITPA genotypes (rs1127354 and rs6051702) and IL28B genotype (rs8099917) were determined by TaqMan SNP assay. We compared clinical background, treatment course and treatment response in terms of these genotypes. Only IL28B rs8099917 major type could predict sustained virological response. ITPA rs1127354 major type leads to significantly greater ribavirin-induced anemia than ITPA rs1127354 minor type between days 0 and 84. We noticed that IL28B rs8099917 minor genotype was associated with higher reduction of neutrophils and platelets. ITPA rs1127354 is useful for the prediction of ribavirin-induced anemia in the early phase after the commencement of peginterferon plus ribavirin treatment and IL28B rs8099917 is useful for the prediction of sustained virological response. Use of the combination of these two genotypes could lead to safe and effective treatment of chronic hepatitis C patients.
Keywords: anemia; HCV; IL28B; ITPA; SNP; sustained virological response
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Miyamura, T.; Kanda, T.; Nakamoto, S.; Wu, S.; Jiang, X.; Arai, M.; Fujiwara, K.; Imazeki, F.; Yokosuka, O. Roles of ITPA and IL28B Genotypes in Chronic Hepatitis C Patients Treated with Peginterferon Plus Ribavirin. Viruses 2012, 4, 1264-1278.
Miyamura T, Kanda T, Nakamoto S, Wu S, Jiang X, Arai M, Fujiwara K, Imazeki F, Yokosuka O. Roles of ITPA and IL28B Genotypes in Chronic Hepatitis C Patients Treated with Peginterferon Plus Ribavirin. Viruses. 2012; 4(8):1264-1278.
Miyamura, Tatsuo; Kanda, Tatsuo; Nakamoto, Shingo; Wu, Shuang; Jiang, Xia; Arai, Makoto; Fujiwara, Keiichi; Imazeki, Fumio; Yokosuka, Osamu. 2012. "Roles of ITPA and IL28B Genotypes in Chronic Hepatitis C Patients Treated with Peginterferon Plus Ribavirin." Viruses 4, no. 8: 1264-1278.