拉米呋啶治疗后乙肝病毒聚合酶YMDD的变异

目的观察拉米呋啶治疗慢性乙肝患者1年前后,患者体内HBV DNA多聚酶结构域C的酪氨酸—甲硫氨酸—天门冬氨酸—天门冬氨酸(YMDD)基因变异情况,及其与血清HBV DNA、丙氨酸氨基转移酶(ALT)水平及乙肝标志物变化的关系。方法采用实时荧光定量PCR、ELISA及速率法分别检测60例乙肝患者经拉米呋啶治疗后其血清YMDD、HBV DNA、乙肝标志物及ALT的变化情况。结果拉米呋啶治疗9月、1年后YMDD的变异率分别为5%、13.3%。YMDD变异组HBV DNA阴转率为12.5%,无变异组HBV DNA阴转率为67.3%,两组阴转率相比差异有统计学意义(P<0.01)。拉米呋啶治疗1年后YMDD变异组ALT为(40.7±14.7)u/L,无变异组ALT为(26.5±10.1)u/L,两组相比差异有统计学意义(P<0.01)。5名HbeAg阴转患者无YMDD变异。结论乙肝患者经拉米呋啶治疗后,YMDD变异率随用药时间的延长可逐渐增加,当其HBV DNA、ALT含量出现明显反跳时,应及早改变治疗方案。

Mutation of YMDD in hepatitis B virus polymerase after lamivudine treatment

Objective To investigate tyrosine-methionine-aspartate-aspartate(YMDD) mutation and the relationship with the levels of HBV DNA,ALT and HbeAg in chronic hepatitis B patients after one year of lamivudine therapy.Methods The serum YMDD mutation,HBV DNA,ALT and HbeAg levels of 60 patients on lamivudine therapy were detected by FQ-PCR,ELISA,and rate method,respectively.Results The occurrence of mutation in the patients was 3.3% and 13.3%,respectively after 9-month and one-year treatment with lamivudine. There was significance difference in the trans-negative ratios of HBV DNA between the patients with and without YMDD mutation(P<0.01).The levels of ALT in the patients with YMDD mutation and without YMDD mutation were(40.7±14.7)u/L and(26.5±10.1)u/L,respectively.The level of ALT in patients with YMDD mutation was higher than that in the patients without YMDD mutations.There was no YMDD mutation in the 5 patients whose HbeAg resurned negative.Conclusion After lamivudine therapy,patients with YMDD mutation showed significant decrease in the level of HBV DNA and ALT.