恩替卡韦治疗拉米夫定失效的慢性乙型肝炎患者5年的临床疗效

Five years trial of entecavir for chronic hepatitis B patients failed with lamivudine therapy in the Chongqing area

目的评价恩替卡韦（ETV）对重庆地区拉米夫定治疗失效的慢性乙型肝炎（CriB）患者5年的疗效和安全性。方法选取拉米夫定治疗失效的CHB患者32例，随机分为ETV组（剂量1．0mg／d）28例和安慰剂组4例，完成12周的双盲治疗后，患者均接受开放的ETV（剂量1．0mg／d）治疗，持续治疗至240周。分别检测治疗2、4、8、12、24、48、96、144、168、240周时患者的血清HBVDNA水平、HBsAg与HBeAg状态和肝功能情况。双盲阶段HBVDNA水平变化情况经Mauchly“球对称”检验后采用重复测量数据方差分析；连续性变量的统计描述用均数±标准差（x±s）表示。结果在接受ETV治疗后，12周时ETV组患者血清HBVDNA水平平均下降4．05log10拷贝／ml，安慰剂组平均下降0．08log10拷贝／ml（P〈0．05）。治疗240周时，ETV组患者HBVDNA水平均值下降至2．58log10拷贝／ml。HBVDNA〈3 log10拷贝／ml患者的百分比在治疗前为0，从第8周开始上升（6．25％），24周时为15．6％，尤其在96周明显上升（50％），到240周末为57．14％。240周末有2例出现HBsAg血清学转换，4例出现HBeAg血清学转换。服用ETV后ALT水平下降较迅速，12周后均数达正常水平，且5年持续低于40U／L。5年治疗期间，患者不良事件发生率为21％，有1例出现严重不良事件。结论ETV（1．0mg／d）治疗拉米夫定失效的CHB患者具有显著的抗病毒和临床疗效，且安全性及耐受性良好。

Objective To evaluate the efficacy and safety of five-year wail of entecavir for chronic hepatitis B patients failed with lamivudine therapy in the Chongqing area. Methods 32 patients failed with lamivudine therapy were enrolled in this study. In the double-blind phase, patients were randomly divided into entecavir 1.0 mg/d group （n = 28） and placebo group（n = 4） for 12 weeks. In the open-lable phase, patients received ETV 1.0 mg/d for 240 weeks. HBV DNA level, liver function, HBV serology were observed. Results The mean reduction in HBV DNA level at week 12 was 4.05 log10 copies/ml in ETV group, and 0.08 log10 copies/ml in placebo group （P 〈 0.05）. The mean of HBV DNA level after 240 weeks of ETV treatment was decreased to 2.58 log10 copies/ml. The proportion of patients with HBV DNA〈 3 log10 copies/ml was 0, 6.25%, 15.6%, 50%, and 57.14% at 0, 8, 24, 96 and 240 weeks respectivfely. There were 2 patients with HBsAg seroconversion and 4 patients with HBeAg seroconversion at the end of the study. The ALT level returned to normal at week 12 and remained normal throughout the following 240 weeks. One patient had a severe adverse event during the trail. Condusion Entecavir is effective and safe for the chronic hepatitis B patients failed with lamivudine therapy.