马来酸恩替卡韦片治疗HBeAg阴性慢性乙型肝炎的随机、双盲、双模拟对照、多中心临床研究48周结果

A randomized, double-blind, double-dummy, controlled, muiticenter study of entecavir maleate versus entecavir for treatment of HBeAg-negative chronic hepatitis B： results at week 48

目的比较马来酸恩替卡韦和恩替卡韦治疗HBeAg阴性慢性乙型肝炎患者的疗效及安全性。方法随机、双盲、双模拟、阳性药对照的多中心临床研究。入选患者随机分为A组和B组，分别接受恩替卡韦片0．5mg／d或马来酸恩替卡韦片0．5mg／d治疗，疗程为48周。于12、24、48周检测血清HBV标志物，定期随访患者，记录不良事件。HBV DNA用罗氏（Cobas Ampliprep／Cobas Taqman）第二代实时PCR法。符合参数分析条件的计量资料采用t检验，等级资料的组间比较用秩和检验，计数资料组间比较采用Fisher’s精确概率法进行统计学分析。结果共入组57例HBeAg阴性慢性乙型肝炎患者，A组26例，二次揭盲后为对照药恩替卡韦，B组31例，二次揭盲后为试验药马来酸恩替卡韦。两组基线各指标具可比性（P〉0．05）。治疗12、24、48周时，A组和B组HBV DNA较基线下降值分别为4．24 log10 IU／ml对比4．01 log10 IU／ml（P〉0．05）、4．61 log10 IU／ml对比4．50 log10 IU／ml（P〉0．05）、4．88 log10 IU／ml对比4．99 log10 IU／ml（P〉0．05）。治疗48周时A组和B组HBV DNA不可测（HBV DNA水平低于20IU／ml）率分别为69．23％和80．65％（P〉0．05），ALT复常率分别为：96．00％对比83．8％（P〉0．05）。不良事件发生率为：22．22%对比9．38％（P〉0．05）。结论马来酸恩替卡韦片与恩替卡韦均能有效治疗HBeAg阴性慢性乙型肝炎，两者疗效和安全性相似。

Objective To evaluate the efficacy and safety of entecavir （ETV） maleate versus ETV in Chinese patients with hepatitis B e antigen （HBeAg）-negative chronic hepatitis B （CHB）. Methods This was a randomized, double-blind, double-dummy, controlled, multicenter study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV （group A; n =26） or 0.5 mg/day ETV maleate （n = 31）. Hepatitis B virus （HBV） DNA levels were measured at weeks 12, 24, and 48 by the Roche Cobas Ampliprep/Taqman PCR assay. Adverse events （AE） were recorded. Results Baseline characteristics were similar between the two groups. At weeks 12, 24, and 48, the mean HBV DNA level had similarly decreased from baseline in both groups （A： by 4.24, 4.61 and 4.88 log10 IU/mL vs. B： 4.01, 4.50 and 4.99 log10 IU/mL, respectively; all P 〉 0.05）. Patients who achieved undetectable levels of serum HBV DNA （〈 20 IU/mL） at week 48 were similar in the two groups （A： 69.23% vs. B： 80.65%; P〉0.05）. Both groups achieved similar normalization of ALT at week 48 （A： 96.00% vs. B： 83.87%; P〉0.05）. The overall AE incidence was similar for the two groups （A： 22.22% vs. B： 9.38%; P〉 0.05）. Conclusion Entecavir maleate and entecavir showed similar efficacy and safety in patients with HBeAg-negative CHB.