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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 study the relationship between multiple variants of HBeAg secretion and HBV YMDD motif during lamivudine treatment of chronic hepatitis B and its clinical significance. Methods Single nucleotide polymorphisms (YMDD), G1896A, A1814C, A176 2T and G176 4A (BCP double mutations) were detected in patients with chronic hepatitis B treated with lamivudine for 9 to 30 months by gene chip technique. Results A total of 22 patients with chronic hepatitis B were treated with lamivudine for 18 months. Twenty-two patients with YMDD mutation occurred in 8 patients, including 3 cases of G1896A, 2 cases of A1814C, 2 cases of G1896A + A1814C and BCP double mutation , BCP double mutation + G1896A multiple mutation in 1 case, simple YMDD mutation and the first 5 cases of combined mutation were HBeAg positive, and then three cases of multiple mutation was HBeAg negative, 1 case of multiple mutations continue treatment for 3 months after the change to simple YMDD wild-type positive, accompanied by HBeAg complex Yang. Conclusions The dominant YMDD and HBeAg-associated multiple variants in lamivudine treatment may be one of the reasons for HBVDNA reversion combined with HBVDNA reversion. Lamivudine treatment should be monitored when HBeAg negative Possible related variations.