Tenofovir disoproxil fumaratevs adefovir dipivoxil in Chinese treatment naive patients with chronic hepatitis B for 48 weeks：a randomized, double-blinded, controlled study

目的：明确国产替诺福韦酯治疗中国慢性乙型肝炎患者的疗效与安全性。方法本研究采取多中心、随机、双盲、阳性对照的研究设计，选择阿德福韦酯为对照。研究的主要疗效指标为治疗48周HBV DNA＜20 IU/ml患者比率；另外，评价患者治疗48周HBV DNA下降水平、ALT复常率、HBsAg阴转及血清学转换率以及HBeAg阳性患者HBeAg阴转及血清学转换率。研究还评价替诺福韦酯与阿德福韦酯治疗组患者的不良事件的发生等情况。结果共入组患者267例，其中替诺福韦酯治疗组（TDF组）141例，阿德福韦酯治疗组（ADV组）139例。两组患者基线人口学指标与临床指标差异均无统计学意义（P均＞0.05）。HBeAg阳性患者中，TDF组患者HBV DNA＜20 IU/ml患者比率显著高于ADV组患者（55.3%vs.20.0%；χ2=20.750，P＜0.001）；同样在HBeAg阳性患者中，TDF组患者HBV DNA＜20 IU/ml患者比率显著高于ADV组患者（86.2%%vs.62.7%%；χ2=20.750，P =0.003）。ALT复常率在HBeAg阳性（84.5%vs.80.5%；χ2=0.406，P=0.524）与阴性CHB患者（84.2%vs.80.7%；χ2=0.243，P =0.622）组中差异均无统计学意义。HBeAg阳性组患者TDF组与ADV组的HBeAg阴转率（5.6%vs.12.8%；χ2=2.335，P =0.126）和HBsAg阴转率（1.4%vs.3.8%；χ2=0.182，P =0.670）差异均无统计学意义。HBeAg阴性组患者无HBsAg阴转病例。TDF组与ADV组患者不良事件和不良反应发生率差异均无统计学意义（P均＞0.05）。结论国产TDF制剂治疗中国HBeAg阳性和阴性的CHB患者抑制HBV效果优于ADV且安全耐受性良好，可作为我国CHB患者的抗病毒治疗首选方案之一。Objective To evaluate the efifcacy and safety proifles of tenofovir disoproxil fumarate (TDF) vs adefovir dipivoxil (ADV) for Chinese patients with chronic hepatitis B (CHB).Methods In this randomized, double-blind, controlled study, patients with CHB received TDF or ADV (ratio for 1︰1) once daily for 48 weeks were assigned, randomly. The primary efficacy end point was plasma HBV DNA level < 20 IU/ml at week 48. The levels of HBV DNA decrease, ratios of ALT normalization, HBsAg loss and seroconversion and HBeAg loss and seroconversion, while the adverse events and adverse effects were also compared between patients in TDF group and ADV group.Results Total of 267 patients were enrolled, among whom, there were 141 patients in TDF group and 139 patients in ADV group. The baseline characteristics were comparable between the two groups (P all > 0.05). At week 48, virological responses occurred in more HBeAg positive patients with TDF treatment than patients with ADV treatment (55.3%vs. 20.0%;χ2= 20.750,P < 0.001) and in more HBeAg negative patients with TDF treatment than patients receiving ADV treatment (86.2%vs. 62.7%;χ2= 20.750,P = 0.003). There were no signiifcant difference in ratio of ALT normalization in both HBeAg positive (84.5%vs. 80.5%;χ2= 0.406,P = 0.524) and negative groups (84.2%vs. 80.7%;χ2= 0.243,P = 0.622). In HBeAg positive group, there were no significant difference in ratio of HBeAg loss (5.6%vs. 12.8%;χ2= 2.335,P = 0.126) and HBsAg loss (1.4%vs. 3.8%;χ2= 0.182,P = 0.670). No case in HBeAg negative group lost HBsAg after 48 weeks therapy. Safety proifles including incidence of adverse events and adverse effects were compared between TDF and ADV groups with no significant difference (P all > 0.05).Conclusions Among Chinese CHB patients with HBeAg positive and negative, TDF had superior antiviral efifcacy with a similar safety proifle compared with ADV through 48 weeks.北京市卫生系统高层次卫生技术人才培养计划(No.2015-3-108)；北京市医院管理局临床医学发展专项经费资助(No. ZY201402)；首都卫生发展科研专项项目中国科技核心期刊(ISTIC)4385-3911