干扰素联合拉米夫定治疗慢性乙型肝炎耐药后HBV YMDD变异及HBV前S2蛋白变化探究.docVIP

干扰素联合拉米夫定治疗慢性乙型肝炎耐药后HBV YMDD变异及HBV前S2蛋白变化探究摘 要 目的：探讨干扰素联合拉米夫定治疗慢性乙型肝炎产生耐药后HBV发生YMDD变异及HBV膜蛋白前S?2的变化。方法：应用实时荧光定量PCR检测联合应用干扰素及拉米夫定治疗慢性乙肝产生耐药后血清中HBV YMDD变异；同时应用ELISA方法检测产生耐药与未产生耐药患者的血清HBV膜蛋白前S?2。结果：产生耐药后突变66例，未突变51例，野生株33例。突变66例中YIDD突变7例；YVDD突变8例；YMDD/YIDD突变12例；YMDD/YVDD突变17例，YMDD/YIDD/YVDD突变22例。产生耐药组HBV-S?2阳性78例，与未产生耐药组(HBV-S?2阳性32例)相比，差异有显著性(P＜0.05)。结论：产生耐药后YMDD发生突变，突变率为44%，以YMDD/YIDD/YVDD突变为主，且HBV-S?2的表达增加，说明耐药后HBV病毒出现活动性复制，发生耐药机制主要为YMDD变异。? 关键词 慢性乙型肝炎 干扰素 拉米夫定 YMDD变异 HBV前S?2蛋白? doi:10.3969/j.issn.1007-614x.2012.02.057?? Abstract Object:To study the YMDD mutation of HBV and the change of the HBVpre-S?2 protein in the resistant chronic hepatitis B patients treated with interferon combined with lamivudine.Method:Real-time fluorescence quantitative PCR method was applied to detect YMDD mutation in the resistant chronic hepatitis B patients treated with interferon combined with lamivudine.ELISA was used to detect the HBV pre-S?2 protein of the drug resistance group and the non-resistant group.Result:There were 66 cases with YMDD mutation after drug resistance,51 cases without mutations,33 cases with wild strains.YIDD mutation were 7 cases,YVDD 8 cases,YMDD/YIDD 12 cases,YMDD/YVDD 17 cases,YMDD/YIDD/YVDD 22 cases in 66 cases with YMDD mutation.There were 32 HBV-S?2 positive cases in non-resistant group,while 78 HBV-S?2 positive cases in drug resistance(P＜0.05).Conclusion:After drug resistance,YMDD mutation occurred.YMDD mutation rate was 44%,and YMDD/YIDD/YVDD was the primary type.Meanwhile,the expression of HBV-S?2 increased.It was suggested that the HBV active replication had emerged again after drug resistance,and YMDD mutation was the primary pathogenesis.? Key Words Chronic Hepatitis B;Interferon;Lamivudine;YMDD mutation;HBV pre-S?2 protein?? 慢性乙型肝炎(CHB)是一种世界广泛流行、严重危害人类健康的传染病，由乙型肝炎病毒(HBV)感染引起，可发展为肝硬化、肝癌等严重肝脏疾病[1]。? 慢性乙型肝炎首选核苷类抗病毒药物拉米夫定及免疫调节剂干扰素治疗已经取得了一定的效果，但单独应用疗效有限，且有一些不良反应，为提高疗效，降低耐药，现临床多采用联合用药[2]，以干扰素联合拉米夫定应用最多。拉米夫定(Lamivudine)又名贺普汀，是胞嘧啶核苷类药物，是目