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慢性乙型肝炎治疗过程中病毒基因变异及临床意义的研究

Gene mutations in chronic hepatitis B treated with lamivudine and alpha interferon
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摘要 目的研究干扰素和拉米夫定治疗慢性乙型肝炎HBV前C区A83点突变及YMDD变异的发生情况,并探讨联合治疗对慢性HBV基因变异的影响。方法90例慢性乙型肝炎病人进行随机化分组,30例肌肉注射干扰素,30例常规口服拉米夫定100mg/d,30例给予拉米夫定和干扰素联合治疗。治疗前检测血清丙氨酸转移酶水平,HBVDNA滴度(定量)水平,前C区A83点突变和YMDD变异,治疗后第1、3、6、9个月分别进行肝功能、HBVDNA定量检测,应用错配聚合酶链反应及限制性片断长度多态性(mPCR-RFLP)检测HBV基因变异的发生情况,对干扰素治疗、拉米夫定治疗和联合治疗后的慢性HBV变异情况进行比较,进行统计学分析。结果干扰素和拉米夫定治疗慢性乙型肝炎都可引起前C区A83点突变和YMDD变异,干扰素引起的变异以前C区A83突变为主,拉米夫定引起的变异以YMDD变异为主,而联合治疗则较少引起HBV变异,差异有统计学意义(P<0.05)。结论HBV变异是药物治疗选择的结果,干扰素、拉米夫定治疗后使变异株成为优势毒株,药效下降,病毒DNA滴度反跳,拉米夫定联合干扰素治疗HBV,基因变异机会则相对较少。 Objective To study the incidence rate of the YMDD mutation and pre C A83 mutation of hepatitis B virus (HBV) in patients with chronic hepatitis B treated with lamivudine or interferon alpha(INFα) either alone or in conbination. Methods Ninety patients with chronic hepatitis B were enrolled and randomized into three groups, 30 cases received interferon alpha , 30 cases received lamivudine, and 30 patients were treated with combined interferon alpha and lamivudine for six months. Levels of serum ALT and HBV DNA were tested after 1,3,6,9 months. Results Both alpha interferon and lamivdine induced YMDD and A83 mutation. Lamivudine combined with interferon alpha treatment caused less mutation ( P 〈 0.05). Conclusion HBV mutations is the result of the medicine treatment that affects the different domain of the virus gene. The hepatitis B gene mutation become the dominent gene after interferon alpha or lamivudine treatment and developed drug resistence. The combination therapy may delay or reduce the occurrence of virus mutation.
出处 《肝脏》 2006年第3期178-180,共3页 Chinese Hepatology
关键词 乙型肝炎 药物治疗 干扰素 拉米夫定 基因变异 Hepatitis B Interferon Lamivudine Gene mutation
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