拉米夫定治疗慢性乙型肝炎过程中HBV YMDD变异株的检测

Detection of HBV YMDD Mutant during the Process of Lamivudine Therapy

目的观察拉米夫定治疗慢性乙型肝炎过程中,乙型肝炎病毒(HBV)发生 YMDD变异的情况;研究HBV YMDD变异的发生率同拉米夫定用药时间及用药前与血清HBV DNA水平的关系;观察拉米夫定治疗过程中,血清HBV DNA水平的变化.方法 80例慢性乙型肝炎病人被分为2组,1组为拉米夫定治疗组50例,另1组为对照组30例.采用实时PCR技术,并结合荧光探针技术,分别检测拉米夫定治疗组和对照组在用药期间的HBV YMDD变异发生率;采用荧光定量PCR技术检测治疗组在用药前及用药期间血清HBV DNA水平.结果治疗组在用药52周时的HBV YMDD变异发生率为24.0%,明显高于对照组用药52周的变异率3.3%(P<0.05); 治疗组在用药52周的HBV YMDD变异率为24.0%,明显高于用药26周时的变异率4.0%(P<0.05);治疗前HBV DNA水平较高组用药52周时的变异率为35.7%,明显高于HBV DNA水平较低组的变异率9.1%(P<0.05);治疗组中未变异组在用药52周时的HBV DNA阴转率为65.8%,明显高于变异组的HBV DNA阴转率16.7%(P<0.05).结论拉米夫定可导致HBV YMDD变异的产生,并且该变异的发生率随着拉米夫定用药时间延长而增加;治疗前血清HBV DNA水平较高者在应用拉米夫定后易发生YMDD变异;HBV YMDD变异发生后,可出现HBV DNA复升,但一般不会超过治疗前的基线水平.

Objective To detect HBV YMDD mutant during the process of lamivudine therapy; To study the relationship between the incidence of HBV YMDD mutant and Lamivudine treatment duration, seral HBV DNA level; To detect the variety of seral HBV DNA level during lamivudine therapy. Methods 80 patients with CHB were divided into two groups. One group was treated with lamivudine, the other group was treated with liver protecting drugs. Real-time PCR and Fluoremetry was used to detect HBV YMDD mutant in therapy group and control group during lamivudine therapy. Fluoremetric quantative PCR was used to detect seral HBV DNA level in therapy group before and during lamivudine therapy. Results The incidence of HBV YMDD mutant after 52 weeks therapy in therapy group （24.0 % ） was significantly higher than that in control group （3.3 % ） （P 〈 0.05）. The incidence of HBV YMDD mutant in therapy group after 52 weeks （24.0 % ） was significantly higher than that after 26 weeks （4.0 % ）（P 〈 0.05）. The incidence of HBV YMDD mutant in higher seral HBV DNA level group （before lamivudine therapy） 35.7 % was significantly higher than that in lower HBV DNA level group（before lamivudine therapy） 9.1% after 52 weeks therapy. The negative conversion rate of HBV DNA in non-YMDD mutant group 65.8% was higher than that in YMDD mutant group 16.7 % after 52 weeks therapy. Conclusion The emergence of HBV YMDD mutant is related to lamivudine and the incidence of HBV YMDD mutant increases with the treatment duration. The patients with high serum HBV DNA level are subject to getting HBV YMDD mutant. The seral HBV DNA levels with YMDD mutant may rise, but they are usually lower than the baseline level before therapy.