Liu Zhenhua, Wang Song, Qi Wenqian, Wang Xu, Sun Derong, Wang Hongguang, Zhang Yonggui, Li Zhongxie, Zhu Liying, Zhao Ping, Guo Honghua, Zhou Changyu, Wang Jiangbin
Department of Digestive of China-Japan Union Hospital affiliated to Jilin University Department of Urology of First Hospital affiliated to Jilin University, Changchun Department of Digestive of the Second Hospital of Daqing Department of Digestive of the People's Hospital of Jilin City Department of Digestive of the People's Hospital of Hunchun City, Jilin Department of Infectious Diseases of the Fourth Hospital of Harbin Medical University, Heilongjiang, China.
Medicine (Baltimore). 2017 Jul;96(29):e7554. doi: 10.1097/MD.0000000000007554.
This prospective study investigated the relationship between 2 inosine triphosphatase (ITPA) polymorphisms (rs7270101 and rs1127354) and the efficacy of ribavirin-based antiviral therapy in hepatitis C virus (HCV)-infected Chinese patients.A total of 906 patients diagnosed with chronic hepatitis C receiving pegylated interferon (PEG-IFN) plus ribavirin combination therapy between January 2011 and January 2014 from 5 hepatitis centers in Northeast China were enrolled. The patients were divided into genotype 1 and non-genotype 1 groups according to the genotype of infected HCV. ITPA single nucleotide polymorphism (SNP) genotyping was performed for all patients. Ribavirin-induced hemolytic anemia and virological response (VR) were monitored during treatment and follow-up. Multivariate regression analysis was used to analyze the predictors for sustained virological response (SVR).IPTA rs7270101 variants were not detected. IPTA rs1127354 variants were detected and showed no difference between the genotype 1 and non-genotype 1 groups. IPTA rs1127354 genotype CC was related to a higher incidence of ribavirin-induced hemolytic anemia. For patients who received >80% of the planned ribavirin dose, rs1127354 variants and related ITPase were related to better SVR. Multivariate analysis showed that IPTA rs1127354 non-genotype CC, HCV genotype, a baseline HCV RNA level <4 × 10 IU/mL, IL-28B rs12979860 genotype CC, and low liver fibrosis were independent predictors for SVR during the combination therapy.IPTA rs1127354 variants and related ITPase were not only related with ribavirin-induced hemolytic anemia but also directly affected the SVR to PEG-IFN plus ribavirin combination therapy in Chinese HCV-infected patients.
这项前瞻性研究调查了2种肌苷三磷酸酶（ITPA）基因多态性（rs7270101和rs1127354）与基于利巴韦林的抗病毒疗法对丙型肝炎病毒（HCV）感染的中国患者疗效之间的关系。2011年1月至2014年1月期间，来自中国东北5个肝病中心的906例被诊断为慢性丙型肝炎且接受聚乙二醇干扰素（PEG-IFN）加利巴韦林联合治疗的患者被纳入研究。根据感染HCV的基因型，将患者分为基因型1组和非基因型1组。对所有患者进行ITPA单核苷酸多态性（SNP）基因分型。在治疗和随访期间监测利巴韦林诱导的溶血性贫血和病毒学应答（VR）。采用多因素回归分析来分析持续病毒学应答（SVR）的预测因素。未检测到ITPA rs7270101变异。检测到ITPA rs1127354变异，且在基因型1组和非基因型1组之间无差异。ITPA rs1127354基因型CC与利巴韦林诱导的溶血性贫血发生率较高相关。对于接受了>80%计划剂量利巴韦林的患者，rs1127354变异和相关的ITP酶与更好的SVR相关。多因素分析显示，在联合治疗期间，ITPA rs1127354非基因型CC、HCV基因型、基线HCV RNA水平<4×10⁶IU/mL、IL-28B rs12979860基因型CC以及低肝纤维化是SVR的独立预测因素。ITPA rs1127354变异和相关的ITP酶不仅与利巴韦林诱导的溶血性贫血相关，还直接影响中国HCV感染患者对PEG-IFN加利巴韦林联合治疗的SVR。
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