拉米夫定治疗慢性乙型肝炎患者YMDD变异及影响因素的研究

Occurrence and predictive factors of hepatitis B virus polymerase YMDD variation among patients with chronic hepatitis B and liver cirrhosis during lamivudine therapy

目的 探讨拉米夫定治疗慢性乙型肝炎(简称慢乙肝)患者过程中YMDD变异的发生率及影响因素。 方法 对采用拉米夫定治疗的249例慢乙肝和64例乙型肝炎肝硬化(简称乙肝肝硬化)患者采用错配聚合酶链反应 限制性片段长度多态性分析的方法检测了乙型肝炎病毒(HBV)多聚酶YMDD变异,并应用SPSS统计软件对YMDD变异发生率和影响YMDD变异发生的因素进行统计学分析。 结果 随治疗时间的延长,YMDD变异的累计发生率逐渐升高;慢乙肝和乙肝肝硬化患者YMDD变异率于12、24、36、48个月分别达8.84％和17.19％、20.91％和32.40％、26.92％和39.56％、26.92％和58.79％。时序检验及Cox回归分折的结果均表明:未联台干扰素治疗,基线丙氨酸氨基转移酶(ALT)水平较低、HBV DNA水平较高和治疗前诊断为肝硬化者均与YMDD变异的较早出现有关(P<0.05)。 结论 拉米夫定治疗慢乙肝患者,未联合干扰素治疗、基线ALT水平较它低、HBV DNA水平较高和乙肝肝硬化可作为YMDD变异发生的预测因子.

Objective To study the incidence and the predictive factors of HBV polymerase YMDD variation among patients with chronic hepatitis B and liver cirrhosis during lamivudine therapy. Methods The clinical data and serial sera of 313 chronic HBV infected patients (249 chronic hepatitis B and 64 liver cirrhosis) treated with lamivudine were collected. YMDD variations were determined by mispairing PCR-RFLP assay. The data were analyzed using SPSS software. Results The cumulative rates of variation among patients with chronic hepatitis B and liver cirrhosis were 8.84% and 17.19%, 20.91% and 32.40%, 26.92% and 39.56%, 26.92% and 58.79% after 12, 24, 36 and 48 months of lamivudine treatment, respectively. The results of log-rank test and Cox's proportional hazard model analysis indicated that lamivudine monotherapy, low ALT level, high HBV DNA level, and the patients with liver cirrhosis at baseline were significantly related to an occurrence of YMDD variation (P < 0.05). Conclusion This study suggests that lower ALT and higher HBV DNA levels at baseline before lamivudine treatment, lamivudine monotherapy without combining α-interferon, and the patients with liver cirrhosis seem to be statistically significant for predicting the occurrence of YMDD variation.