背景及目的：恩替卡韦与替诺福韦酯是较为公认的强效抗病毒药物，并且可以在慢性乙型肝炎的治疗中起到协同作用，本研究旨在对恩替卡韦单药治疗与恩替卡韦联合替诺福韦酯治疗进行疗效比较。方法：我们对379名使用核苷类似物进行初治的慢性乙型肝炎感染者进行了一项随机的、开放的、多中心的、前瞻性研究，纳入者中包括e抗原阳性者(n = 264) 和e抗原阴性者(n = 115)。受试者给予为期100周的恩替卡韦（0.5 mg）或是恩替卡韦0.5 mg与替诺福韦酯300 mg进行联合治疗。在治疗后的第96周，两组中均有相当比例的患者达到了抗病毒治疗的病毒学终点，HBV DNA <50 IU/mL (83.2% vs 76.4%; P = .088)。在e抗原阳性组的患者中，与单药治疗者相比，接受联合治疗的患者中有更多的个体获得了病毒学应答HBV DNA <50 IU/mL (80.4% vs 69.8%; P = .046)，然而，这一现象只是在治疗基线HBV DNA ≥ 10⁸ IU/mL (79% vs 62%)的患者中出现，当HBV DNA <10⁸ IU/mL (单药治疗及联合治疗者均为83%)没有类似的情况发生。e抗原的消失率以及e抗原的血清学转化率在两组间的比例相似，而转氨酶水平转为正常在单药治疗组更为明显。在本研究中没有发现针对恩替卡韦或是替诺福韦酯的乙肝病毒变异位点，治疗的安全性与之前所报道的恩替卡韦或是替诺福韦酯单药治疗的安全性相一致。结论：恩替卡韦单药治疗与恩替卡韦联合替诺福韦酯治疗的抗病毒效果在一组混合的(70% HBeAg 阳性)慢性乙肝感染初治患者中的疗效相似，联合治疗对于治疗基线时HBV DNA ≥ 10⁸ IU/mL的e抗原阳性感染者更为有益。

                                   吉林大学第一医院 肝胆胰内科 张明媛 摘译

本文首次发表于[Gastroenterology. 2012,143(3):619-628.e1]

Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos(t)ide-naïve patients with chronic hepatitis B.

BACKGROUND AIMS: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are potent antiviral agents that might have additive or synergistic antiviral activity in treatment of patients with chronic hepatitis B (CHB). We compared the efficacy and safety of ETV monotherapy with those of a combination of ETV and TDF. METHODS: We performed a randomized, open-label, multicenter, superiority study of 379 nucleos(t)ide-naïve patients with hepatitis B e antigen (HBeAg)-positive (n = 264) or HBeAg-negative (n = 115) CHB. Subjects were given ETV 0.5 mg (n = 182) or a combination of ETV 0.5 mg and TDF 300 mg (n = 197) for 100 weeks. RESULTS: At week 96, comparable proportions of patients in each study arm achieved the primary end point of a level of hepatitis B virus (HBV) DNA <50 IU/mL (83.2% vs 76.4%; P = .088). Among HBeAg-positive patients, a greater proportion given combination therapy achieved levels of HBV DNA <50 IU/mL than those given ETV alone (80.4% vs 69.8%; P = .046). However, this difference was observed only in patients with baseline levels of HBV DNA ≥ 10(8) IU/mL (79% vs 62%) and not in those with baseline levels of HBV DNA <10(8) IU/mL (83% in both arms). Rates of HBeAg loss and HBeAg seroconversion were comparable between groups, whereas the rate of alanine aminotransferase normalization was greater in the ETV monotherapy group. No HBV variants associated with ETV or TDF resistance were detected. Safety profiles were consistent with previous reports of ETV or TDF monotherapy. CONCLUSIONS: The antiviral efficacy of ETV monotherapy is comparable to that of ETV plus TDF in a mixed population of nucleos(t)ide-naïve patients with CHB (70% HBeAg positive). The combination therapy could provide an incremental benefit to HBeAg-positive patients with baseline levels of HBV DNA ≥ 10(8) IU/mL.点击下载此文件