拉米夫定治疗慢性乙型肝炎发生YMDD变异的研究

Study on YMDD mutation during Lamivudine therapy of chronic hepatitis B

目的探讨拉米夫定治疗慢性乙型肝炎(CHB)发生YMDD变异的临床意义。方法分别用荧光定量PCR、ELISA检测72例用拉米夫定治疗的CHB患者治疗前(0个月)、治疗中(9、12、18个月)YMDD变异的情况、HBVDNA定量水平、两对半等指标。结果72例CHB患者中,拉米夫定治疗前未检查出YMDD变异,治疗9、12、18个月分别检出YMDD变异8例(11.1%),17例(23.6%),28例(38.9%),随治疗时间的延长,YMDD变异率升高(P<0.05)。另外用药前HBVDNA定量>108copies/ml与HBVDNA定量<108copies/ml相比YMDD变异率显著升高(P<0.005)。HBeAg阳性组与HBeAg阴性组的患者在不同治疗时间YMDD变异率,差异无显著性(P>0.05)。结论YMDD变异的发生随治疗时间的延长而增加。血清病毒载量可作为应用拉米夫定治疗YMDD变异产生的早期预测指标。

Objective To investigate the clinical significance of YMDD mutation during Lamivudine therapy on chronic hepatitis B. Methods Fluorometric analysis PCR, ELISA were used to estimate the YMDD mutation, HBVDNA quantative level and HBeAg for HBV of 72 cases with chronic hepatitis B before therapy （0 month） , and ＇after Lamivudine therapy for 9,12,18 months. Results The YMDD mutation was not observed in these cases before Lamivudine therapy. The mutation was found in8eases （11.1%）, 17 cases （23.6%） and 28 eases （38.9%） at 9, 12, 18 month for therapy. The YMDD mutation rate rose with the therapy time lasting （P 〈 0. 05）. Moreover, the YmDD mutation rate in the patients with HBVDNA quantity higher than l0s copies/ml was significantly higher than that in the patients with HBVDNA quantity lower than 108 eopies/ml （P 〈 0. 005 ）. The YMDD variation rate in patients with HBeAg positive and in patients with HBeAg negative showed no significant difference （P 〉 0.05）. The HBeAg negative conversion rate was significantly higher in non - mutation group than that in nmtation group （ P 〈 0. 05 ）. Conclusion The serum virus quantity may be regard as an early estimate indication of the development of YMDD mutation during Lamivudine therapy.