实时荧光定量聚合酶链反应技术检测乙型肝炎病毒YMDD变异的临床应用及意义

目的检测慢性乙型肝炎（CHB）患者在使用拉米夫定过程中，乙型肝炎病毒YMDD变异的发生情况并分析与YMDD变异发生的相关因素。方法110例慢性乙肝患者作为拉米夫定治疗组，30例CHB患者作为对照组。采用实时荧光PCR方法分别检测两组患者在用药期间HBV-YMDD变异的发生情况，同时检测治疗组在用药前后的HBV-DNA水平。结果治疗组在48周时的变异率为22．7％，明显高于对照组3．3％及24周时的变异率3．6％（P均〈0．05）；治疗前HBV-DNA水平较高组（47例）患者用药48周时的变异率（31．9％）明显高于HBV—DNA水平较低组（29例）患者的变异率（10．3％）（P〈0．05）；治疗组中未变异的85例患者在48周时的HBV—DNA阴转率（74．1％）明显高于变异的25例患者HBV—DNA阴转率（16．0％）（P〈0．05）。结论拉米夫定可导致HBV-YMDD变异的产生，且变异的发生率随着用药时间的延长而增加；HBV-YMDD变异的发生同HBV—DNA水平关系密切。

Clinical practice and significance of HBV-YMDD variation using real-time fluorescence polymerase chain reaction

Objective To detect hepatitis B virus （HBV） YMDD variation of chronic hepatitis B （CHB） patients during lamivudine therapy and to investigate the factors related to the development of HBV-YMDD variation. Methods One hundred and ten patients were selected as lamivudine therapy group and 30 patients as control group. Real-time fluorence PCR was used to detect HBV-YMDD variation in the two groups. Fluoremetric quantitative PCR was used to detect serum HBV-DNA level in therapy group before and during lamivodine therapy. Results The incidence of HBV-YMDD variation in therapy group after 48 weeks therapy （22.7%） was significantly higher than that in control group （3.3%） （P 〈0.05）. The incidence of HBV-YMDD variation in therapy group after 48 weeks therapy（22.7% ） was higher than that after 24 weeks therapy （3.6%） （ P 〈 0.05 ）. The incidence of HBV-YMDD variation in higher serum HBV-DNA level group（31.9% ） was significantly higher than that in lower HBV-DNA group （ 10.3% ） （P 〈 0.05 ）. The negative conversion rate of HBV-DNA in non-YMDD variation group （74.1% ） was higher than that in HBV-YMDD variation group （ 16.0% ） （P 〈 0.05）. Conclusion HBV-YMDD variation is related to lamivudine and increased with the treatment duration. The patients with high serum HBV-DNA level are subject to get HBV-YMDD variation.