乙型肝炎病毒基因型、YMDD变异与拉米夫定治疗后HBV DNA反弹关系的研究  

The relationship of hepatitis B virus genotypes,YMDD mutations in hepatitis B patients with HBV DNA rebound after lamivudine therapy

作　　者：苏明华[1] 周元平[2] 江建宁[1] 陈茂伟[1] 刘志红[1] 

机构地区：[1]广西医科大学第一附属医院感染性疾病科,530021 [2]广州南方医院,海南医学院附属医院

出　　处：《实用肝脏病杂志》2008年第3期154-156,共3页Journal of Practical Hepatology

基　　金：广西壮族自治区自然科学基金资助项目(桂科回0342009);广西卫生厅课题资助(Z2003043);海南省自然科学基金资助(80579)

摘　　要：目的探讨HBV基因型、YMDD变异与拉米夫定抗病毒治疗后HBV DNA反弹的关系。方法应用多引物对巢式PCR法、PCR-序列分析法检测拉米夫定治疗的27例乙型肝炎患者和19例从未用过抗病毒治疗的患者HBV基因型和P区(YMDD)的突变位点。结果在27例HBV DNA反弹的患者中,13例(48.15%)检出YMDD变异,而对照人群无YMDD变异(P<0.05)。YMDD变异的位点为rtM204V/(IC区)±rtL180M(B区);在治疗组YMDD变异的患者中,B、C基因型构成比(46.15%和59.26%)与对照组(53.85%和68.42%)比较无显著性差异(P>0.05)。结论YMDD变异是拉米夫定治疗后出现耐药导致HBV DNA反弹的主要原因;YMDD变异的常见位点依然为rtM204V/I(C区)±rtL180M(B区);YMDD变异在B、C基因型病人中无差别。Objective To investigate the relationship of hepatitis B virus genotypes,gene mutations and mutated spot in patients with HBV DNA rebound after lamivudine therapy. Methods Twenty-seven hepatitis B patients with HBV DNA rebound after lamivudine therapy and 19 patients without antiviral therapy were investigated. HBV genotype was detected by nested PCR with multiple pair primers. Mutations of YMDD were identified by PCR gene sequence analysis in sera of 27 patients after HBV DNA rebound,and in sera of 4 patients before therapy in the therapy group and in sera of 19 patients in the control group. Results The rate of YMDD mutations in serum of patients with HBV DNA rebound was 48.15%（13/27）,much higher than 0%（0/19） in the control group （P〈0.01）;The location of the YMDD mutation was rtM204I/V （domain C）±rtL180M （domain B）according to the new nomenclature. In patients with the YMDD mutation,the genotype B and C were 46.15% and 53.85%,respectively,not significandy different as compare with the control group（P〉 0.05）. Conclusion YMDD mutation is the most important reason for HBV DNA rebound after lamivudine therapy. The common site of the YMDD mutation is rtM204I/V（domain C）±rtL180M（domain B）.

关 键 词：乙型肝炎 基因型 YMDD变异 拉米夫定 HBV DNA反弹 

分 类 号：R512.62[医药卫生—内科学] R373.21[医药卫生—临床医学]