拉米夫定治疗乙型肝炎后病毒YMDD变异与HBV-DNA基线水平的关系

The Relation of HBV YMDD Variation and Baseline HBV-DNA in the Patients with Chronic Hepatitis B Treated with Lamivudine

目的探讨拉米夫定治疗乙型肝炎后病毒YMDD变异与治疗前HBV-DNA基线水平的关系。方法32例慢性乙型肝炎患者采用拉米夫定片,100 mg/次,口服,1次/d,并随访1年。于治疗后第3、6、9、12个月采用全自动生化分析仪检测肝功能,用ELISA方法检测HBV-M水平,用荧光定量PCR方法检测HBV-DNA水平,用PCR-RFLP方法检测YMDD变异。结果拉米夫定治疗12个月,HBV-DNA转阴率71.88%(23/32),HBeAg转阴率25.93%(7/27),HBeAg/HBeAb血清转换率18.52%(5/27),ALT复常率62.50%(20/32);治疗前ALT水平为(132.59±66.07)U/L,治疗6个月ALT水平为(46.28±17.89)U/L,治疗12个月ALT水平为(49.78±27.94)U/L,治疗前与治疗6、12个月比较,均有非常显著性差异(P均<0.001);32例患者在治疗前均未发现YMDD变异,治疗12个月发现5例YMDD变异,一年期总变异率15.63%,其中DNA<106copies/mL组1例,变异率为5.88%,DNA≥106copies/mL组4例,变异率26.67%,两组之间无显著性差异(P=0.161)。结论治疗前HBV-DNA水平不能预见YMDD变异的发生;随着拉米夫定用药时间的延长,出现变异株的病例增加;变异株被检出时HBV-DNA水平均未超过用药前的水平。

Objective To evaluate the relation of HBV YMDD variation and baseline HBV- DNA in the patients with chronic Hepatitis B treated with Lamivudine. Methods Thirty-two patients were randomly selected, prescribed lamivudine tablet for them at the oral dose of 100rag once daily and followed-up for one year. The liver function and HBV virology including HBV- DNA level, HBV marker,YMDD variation were tested every three months. Results After treatmented for 12 months with lamivudine the negative conversion rate of serum HBV-DNA, the negative conversion rate of HBeAg, the seroconversion rate of HBeAg/HBeAb and normalization rate of ALT were 71.88% （23/32）, 25. 93% （7/27）, 18.52% （5/27）, 62.50% （20/32） respectively. The level of ALT before treatment was （132.59±66.07）U/L. The level of ALT after 6 months treatment with lamivudine was （46.28±17.89） U/L. The level of ALT after 12 months treatment with lamivudine was （49.78±27.94）U/L（P〈（0.001）. No YMDD variation was detected before treatment in 32 patients. Five YMDD variations were detected in one year. （1 in GROUP Ⅰ and 4 in GROUP Ⅱ ） The rate of mutation were 5.88% and 26.67% in groupⅠ and group Ⅱ respectively（P=0. 161）. No statistically significant diffirence was showed. Conclusion The HBV-DNA level of pre-therapy are not enough to predict the YMDD mutation. The prolonged lamivudine therapy would increase the incidence of HBV YMDD variation.