慢性乙型肝炎患者拉米夫定治疗24周时YMDD变异对疗效的影响

Efficacy changes of short-term lamivudine therapy for chronic hepatitis B with emergence of YMDD mutation

目的 使用基因芯片方法检测乙型肝炎病毒(HBV)YMDD变异的发生情况,研究YMDD变异发生与肝功能损伤和HBV复制水平指标之间的关系。方法 120例以常规剂量(100mg/d)口服拉米夫定的慢性乙型肝炎患者,治疗前和治疗第24周抽取血清检测丙氨酸氨基转移酶(ALT)、HBV DNA(定量)水平,对24周HBV DNA阳性的17例患者血清样本,以基因芯片方法检测其治疗前和治疗24周时血清中YMDD变异是否存在,并分析该变异发生和ALT、HBV DNA的关系。结果 (1)120例入选患者治疗24周时有17例患者HBV DNA仍为阳性,除外治疗前已存在的1例感染变异病毒,基因芯片共检出7例变异,变异率为5.8％。其中纯变异2例,YIDD变异1例,YVDD变异1例,混合变异5例,其中YMDD/YVDD变异3例,YVDD/YMDD变异2例。(2)变异组在治疗前和治疗24周时ALT定量水平与非变异组相比,差异无显著性,P>0.05。(3)变异组在治疗前和治疗24周时HBV DNA定量水平与非变异组相比,差异无显著性,P>0.05。结论 在拉米夫定治疗过程中,YMDD基因变异发生对肝脏炎症活动度和病毒复制的抑制作用无显著影响。

Objective To investigate the relationship between curative effect and incidence rate of the YMDD mutations of hepatitis B virus during lamivudine treatment for chronic hepatitis B patients twenty-four weeks. Methods 120 patients with chronic hepatitis B were treated with lamivudine (100 mg/d) over 24 weeks. The levels of serum ALT and HBV DNA and clinical symptoms were detected at baseline and the 24th weeks after treatment. HBV DNA YMDD mutation in 17 patients was detected by gene chips at baseline and the 24th weeks. Results (1) Beside I case of YMDD/ YVDD mutation was found before lamivudine treatment, 7 mutation were found after 24 weeks treatment, 2 with pure mutation strain, one of them was YIDD mutation, and the other was YVDD mutation; 2 and 3 others were YVDD/YMDD mutations and YMDD/YVDD mutations respectively. (2) The serum ALT and HBV DNA levels of YMDD mutation group showed no significantly change compared with normal group at baseline and 24th week (P<0.05). Conclusion The level of serum ALT and HBV DNA showed no significantly changes with the incidence of YMDD mutations at the 24 week treatment (P<0.05).