Gastroenterology:HCV3型患者索非布韦治疗响应低相关因素研究

2019-09-02 MedSci MedSci原创

研究认为一种常见的多态性,即丙型肝炎病毒3a NS5b聚合酶150位的V,与其他变异相结合,降低了对Sofosbuvir的病毒应答

索非布韦是一种常用的丙型肝炎病毒(HCV)聚合酶的泛基因型抑制剂,对多种慢性HCV感染有效,但HCV3型患者使用索非布韦的效果较其他基因型较差。研究人员收集了来自英国国家卫生服务计划的数据,以考察与索非布韦治疗失败相关的病毒因素。

研究人员收集了14例丙型肝炎病毒(HCV)3型患者的血清样本,对其进行索非布韦病毒敏感性评价。鉴定了与应答降低相关的多态性,并测试了其对索非布韦和利巴韦林的敏感性。研究人员对另外411例慢性丙型肝炎病毒(HCV)基因3型感染患者进行多因素Logistic回归分析,探讨其与持续病毒学反应的关系。

研究人员发现HCV基因型3a患者NS5B聚合酶氨基酸150丙氨酸(A)替换为缬氨酸(V),在42%的患者中观察到150位点的V,导致对索非布韦的治疗响应降低。在使用含索非布韦的方案治疗的患者中,A-V150变异体与使用索非布韦和利巴韦林治疗的反应减少有关。在326例V150患者中,71%的患者获得了持续的病毒学反应,而A150为88%。细胞模型中, V150是病毒治疗敏感性下降了7倍。研究发现,另一种罕见突变,即谷氨酸(E)206,显著降低了对索非布韦的敏感性(8.34倍),而V 150合并E 206可降低了病毒对索非布韦的反应35.77倍。

研究认为一种常见的多态性,即丙型肝炎病毒3a NS5b聚合酶150位的V,与其他变异相结合,降低了对Sofosbuvir的病毒应答。

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    2019-12-15 许安
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    2019-09-04 ymljack
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