恩替卡韦抗乙型肝炎病毒感染量效关系及安全性的研究

目的:探讨恩替卡韦(ETV)治疗慢性乙型肝炎抗病毒感染的量效关系及安全性。方法:采用随机、双盲、安慰剂对照的临床试验,选择未经抗病毒治疗的慢性乙型肝炎病毒(HBV)感染者,按1:1:1的比例分为3组:ETV0.5mg/d组、ETV0.1mg/d组和安慰剂组,治疗28d,停药观察56d,然后用ETV0.5mg/d开放治疗48周,再次停药观察24周。结果:ETV0.5mg/d的疗效优于0.1mg/d,停药后HBV DNA的反跳也较缓慢。开放治疗期间有81.6%的受试者HBV DNA<0.7mmol/ml,HBeAg/抗HBe的血清转换率为7.9%,但停药后80%的受试者HBV DNA再度升高。给药组和安慰剂组受试者不良事件发生率无统计学差异(P=0.428),开放治疗期间未发现与恩替卡韦相关的严重不良反应。结论:ETV有较强的抗HBV活性,其抗病毒作用与剂量相关。恩替卡韦0.5mg/d治疗慢性乙型肝炎更为有效和安全。

Studies on dose-response relationship and safety of entecavir for treating hepatitis B virus infection

Objective: To evaluate the dose-response relationship and safety of entecavir for treating chronic hepatitis B virus infection. Methods: In a randomized, double-blind, placebo-controlled study, the patients with hepatitis B virus infection and without previous antiviral therapy were assigned to following 3 groups in the ratio of one to one to one: entecavir 0.5 mg/d group, entecavir 0.1 mg/d group, and placebo group. The patients were treated for 28 d. The postdosing follow-up was 56 d. And then the patients in the three groups were treated with entecavir 0.5 mg/d during the 48 weeks open-label treatment phase of the study. The postdosing follow-up was 24 weeks. Results: The entecavir 0.5 mg/d had more potent antiviral activity than that of entecavir 0.1 mg/d, and the HBV DNA breakthrough was slower after discontinuation of the drug. In the end of open-label treatment phase, the HBV DNA levels were decreased to < 0.7 mmol/ml in 81.6% patients, and the rate of HBeAg/anti-HBe seroconversion was 7.9%. But the HBV DNA levels were increased again in 80% patients after the drug withdrawal. There were no statistically differences (P=0.428) in the incidence of adverse events between the entecavir therapy group and placebo group, the serious adverse reactions related to the entecavir were not found during the open-label treatment phase. Conclusion: Entecavir has potent antiviral activity against HBV, and its antiviral effect is related to the dosage. The entecavir 0.5 mg/d is more effective and safer in treating patients with chronic hepatitis B virus infection.