摘要
目的评价恩替卡韦(ETV)对拉米夫定(LVD)失效的慢性乙型肝炎(CHB)患者治疗1年的疗效和安全性。方法选择LVD治疗失效的CHB患者145例,按4：1比例随机分为ETV组(1．0mg/d)116例和安慰剂组29例,治疗12周后,所有患者进入36周的开放用药阶段(ETV 1．0 mg/d)。观察血清HBV DNA水平、乙型肝炎e抗原(HBeAg)、肝生化功能的变化和不良事件的发生率。结果经12周的治疗,ETV组患者血清HBV DNA平均下降4．30 log_(10)拷贝/ml(聚合酶链反应法),安慰剂组下降0．15 log_(10)拷贝/ml(P＜0．01)。第12周时,在基线丙氨酸转氨酶(ALT)异常的患者中,ETV组的ALT复常率明显高于安慰剂组(分别为68%与6%,P＜0．01)。两组间不良事件的总发生率相当(33%与28%)。经48周的治疗,服用ETV 48周患者HBV DNA的下降幅度为5．08 log_(10)拷贝/ml；服用ETV 36周患者HBV DNA的下降幅度为4．86 log_(10)拷贝/ml；在治疗前ALT异常的患者中,上述两组ALT的复常率分别是85%和90%。治疗结束时,在基线HBeAg阳性的患者中,有6．2%(8/129)出现血清学转换。在治疗期间,未发生与耐药相关的变异。每天服用ETV 1．0mg,持续48周的安全性和耐受性良好。结论ETV(1．0 mg/d)治疗LVD失效的CHB患者具有显著的抗病毒和临床疗效。
Objective Evaluation of safety and efficacy of one year treatment of entecavir （ETV） in Chinese patients with chronic hepatitis B （CHB） who had failed to lamivudine（LVD） treatment. Methods One hundred and forty-five eligible patients were enrolled who had documented LVD failure. In the double-blind phase, patients were randomized（4 ： 1） to ETV 1.0 mg/d（n = 116） or placebo（n = 29） for 12 weeks. In the open-label phase, all patients received ETV 1.0 mg/d for 36 weeks. HBV DNA level, liver biochemical tests, HBV seromarkers and safety assessments were conducted. Results The mean reduction in HBV DNA levels at week 12 was 4.30 log10 copies/ml in ETV group compared to 0.15 log10 copies/ml in placebo group（P 〈 0.01 ）. Among patients with abnormal alanine aminotransferase （ALT） at baseline, a significantly higher percentage of patients in the ETV group had achieved ALT normalization at week 12 than in the placebo group（68% vs 6%, P〈 0.01）. In 12 weeks period, the overall incidence of adverse events was comparable between treatment groups; 33% of ETV patients and 28% of placebo patients reported adverse events. All patients treated in the double-blind phase entered the open-label dosing phase. Among patients initially treated with ETV in the double-blind phase, the mean reduction in HBV DNA levels after 48 weeks of ETV treatment was 5.08 log10 copies/ml. In patients initially treated with placebo in double-blind phase, the mean reduction in HBV DNA levels after 36 weeks of ETV treatment was 4.86 log10 copies/ml. Normalization of ALT levels was observed in more than 85% of patients with abnormal ALT at baseline. HBeAg seroconversion occurred in 6.2%（8/129） at week 48. No mutations associated with resistance to ETV were detected. ETV 1.0 mg per day for up to 48 weeks was safe and well tolerated. Conclusions The findings from this study demonstrated the antiviral activity and safety of ETV in adults with CHB who have failed LVD.
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2006年第6期385-389,共5页
Chinese Journal of Infectious Diseases
