乙型肝炎病毒YMDD及e抗原相关多重变异及其临床意义  

Emergence and clinical significance of YMDD and HBeAg-related mutations during lamivudine treatment

作　　者：许东[1] 田德英[1] 王卫华[1] 陈红云[1] 邢铭友[1] 郭威[1] 宋佩辉[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院传染科,武汉430030

出　　处：《中华内科杂志》2004年第2期121-124,共4页Chinese Journal of Internal Medicine

摘　　要：目的　研究拉米夫定治疗慢性乙型肝炎期间HBVYMDD基序、影响HBeAg分泌的多重变异情况与临床的关系。方法　采用基因芯片技术对拉米夫定治疗 9～ 30个月的慢性乙型肝炎患者进行YMDD基序、G1896A、A1814C、A176 2T和G176 4A(BCP双突变 )单碱基变异检测。结果　 10 2例慢性乙型肝炎患者拉米夫定平均治疗 18个月时 ,2 2例发生YMDD变异 ,其中 8例发生多重变异 ,包括G1896A 3例、A1814C 2例、G1896A +A1814C、BCP双突变、BCP双突变 +G1896A多重变异各 1例 ,单纯YMDD变异和前 5例联合变异均为HBeAg阳性 ,而后 3例多重变异则为HBeAg阴性 ,其中 1例多重变异继续治疗 3个月后转变为单纯YMDD野生株阳性 ,同时伴有HBeAg的复阳。结论　拉米夫定治疗过程中存在YMDD及HBeAg相关多重变异的优势病毒株可能是HBVDNA复阳、同时伴有HBeAg阴转的原因之一 ,拉米夫定治疗过程中 ,HBeAg阴性时应监测其可能的相关变异。Objective To explore YMDD and HBeAg related mutations of hepatitis B virus and its clinical significance during lamivudine therapy. Methods From sera of chronic hepatitis B patients with 9-30 months lamivudine therapy, signal-base mutations of YMDD motif, G1896A, A1814C, A1762T and G1764A were analyzed by gene chips technique. Results In the 102 patients with 18 months in average of lamivudine treatment, 22 were found to have YMDD mutations, including 8 with YMDD and HBeAg related mutants. 3 of the 8 patients had G1896A mutant, 2 had A1814C and the remaining had G1896A+A1814C, A1762T and G1764A , A1762T and G1764A + G1896A. The former 5 patients and signal YMDD mutant patients were HBeAg positive, while the latter 3 with YMDD and HBeAg related multiple mutants were HBeAg negative. One of the three patients with multiple mutants who continued lamivudine treatment 3 months more reversed to YMDD wide-type HBV with accompanying positive HBeAg. Conclusions Mutant of YMDD associated with HBeAg related multiple mutations during lamivudine treatment may arise in patients with HBV DNA breakthrough and negative HBeAg. HBV DNA should be detected in the patients with HBeAg seroconversion to exclude the HBeAg related multiple mutations.

关 键 词：乙型肝炎病毒 YMDD E抗原 基因变异 拉米夫定 药物治疗 

分 类 号：R512.6[医药卫生—内科学]