Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
Viruses. 2012 Aug;4(8):1264-78. doi: 10.3390/v4081264. Epub 2012 Aug 14.
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.
据报道,肌苷三磷酸酶(ITPA)基因变异可预防接受慢性丙型肝炎治疗的患者发生利巴韦林诱导性贫血。IL28B 变异也会影响这些患者接受聚乙二醇干扰素加利巴韦林治疗的应答反应。在本研究中,我们研究了 ITPA 和 IL28B 基因型如何对接受聚乙二醇干扰素加利巴韦林治疗的 HCV 感染患者的治疗诱导性血液毒性和治疗应答产生临床影响。通过 TaqMan SNP 检测法确定 ITPA 基因型(rs1127354 和 rs6051702)和 IL28B 基因型(rs8099917)。我们根据这些基因型比较了临床背景、治疗过程和治疗应答。只有 IL28B rs8099917 主要基因型可以预测持续病毒学应答。与 ITPA rs1127354 次要基因型相比,ITPA rs1127354 主要基因型在第 0 天至第 84 天导致利巴韦林诱导性贫血的发生率显著更高。我们注意到,IL28B rs8099917 次要基因型与中性粒细胞和血小板减少幅度更大有关。ITPA rs1127354 可用于预测聚乙二醇干扰素加利巴韦林治疗开始后早期的利巴韦林诱导性贫血,而 IL28B rs8099917 可用于预测持续病毒学应答。联合使用这两种基因型可实现丙型肝炎患者的安全有效治疗。