阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎的临床研究

 

王宇明 陈耀凯 张大志 雷秉钧 陆志檬 尹有宽 俞云松

 

【摘要】  目的  研究阿德福韦酯片对拉米夫定耐药慢性乙型肝炎患者的疗效和安全性。 方法  采用多中心、随机、双盲双模拟、拉米夫定对照的临床试验，选择拉米夫定耐药的HBeAg阳性慢性乙型肝炎患者209例，按1∶1的比例随机分为阿德福韦酯组105例，拉米夫定组104例。完成24周和48周治疗时，检测血清HBV DNA水平、乙型肝炎病毒血清学标志物及肝功能变化。 结果  治疗24周时阿德福韦酯组血清HBV DNA水平，平均下降2.40 log10，病毒应答率为59.0%，丙氨酸氨基转移酶（ALT）复常率为54.3%，均显著高于拉米夫定组；治疗48周时阿德福韦酯组血清HBV DNA水平，平均下降2.71log10，病毒应答率为61.9％，ALT复常率为54.3％，显著优于拉米夫定组；阿德福韦酯组治疗后血清HBeAg阴转率、HBeAg血清转换率及不良事件发生率与拉米夫定组相比，差异无统计学意义。未发生与研究药物相关的严重不良反应。 结论  阿德福韦酯片治疗拉米夫定耐药慢性乙型肝炎，可在病毒学及生物化学方面取得较好疗效，且安全性良好。

【关键词】  肝炎，乙型，慢性； 临床试验； 拉米夫定； 抗药性； 阿德福韦酯

 

【Abstract】    Objective    To investigate the efficacy and safety of adefovir dipivoxil (ADV, DAIDINGTM) for Chinese chronic hepatitis B patients with lamivudine (LAM) resistance. Methods    This study was a multicenter, double-blind clinical trial. 209 chronic hepatitis B patients with LAM resistance were ramdomly put in an ADV, DAIDINGTM or a LAM group. After 24 and 48-weeks of treatment, serum HBV DNA levels were measured by quantitative PCR and liver function tests; HBV serology and safety assessments were also conducted. Results    The mean reduction of HBV DNA from baseline at 24 and 48 weeks was significantly greater in the ADV group compared with that in the LAM group (2.40 log10 vs 0.94 log10, P < 0.01; 2.71 log10 vs 1.07 log10, P < 0.01). In the ADV group, the virological response and ALT normalization at 24 and 48 weeks were significantly higher than those in the LAM group. There was no significant difference between the two groups in the portion of HBeAg reduction, HBeAg seroconversion and incidence of adverse events. There was no severe adverse event related to the investigational product, DAIDINGTM, in this trial. Conclusion    DAIDINGTM (ADV) is effective and safe for the treatment of chronic hepatitis B patients with LAM resistance.

【Key words】     Hepatitis B, chronic;   Clinical trial;   Lamivudine;   Drug resistance;    Adefovir dipivoxil