Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
J Hepatol. 2010 Jun;52(6):791-9. doi: 10.1016/j.jhep.2009.12.036. Epub 2010 Mar 24.
BACKGROUND & AIMS: To evaluate the long-term efficacy of entecavir in nucleoside-naïve chronic hepatitis B patients.
One hundred and sixty-seven patients treated with entecavir 0.01mg, 0.1mg or 0.5mg for 24-52weeks in Phase II studies entered rollover study ETV-060 and received entecavir 0.5mg daily. Responses were evaluated among patients with available samples.
After 96weeks in ETV-060 (120-148weeks total entecavir treatment time), 88% (127/144) of patients had HBV-DNA <400 copies/ml; 90.1% (128/142) had alanine aminotransferase (ALT) 1x the upper limit of normal (ULN) among those with abnormal baseline ALT; and 26% (32/121) achieved HBe seroconversion among those HBeAg(+) at baseline. A subset of 66 patients received entecavir 0.5mg (approved dose) from Phase II baseline: at week 96 in ETV-060, 83% (48/58) had HBV-DNA <400 copies/ml, 88% (52/59) had ALT 1x ULN, and 20% (10/49) achieved HBe seroconversion. Twenty-one out of 66 patients had paired baseline and on-treatment biopsies: 100% (21/21) and 57% (12/21) demonstrated histologic improvement, and improvement in fibrosis, respectively, over 3years. The 3-year cumulative probability of resistance was 3.3% for all patients and 1.7% for the 0.5mg subset.
Long-term entecavir for nucleoside-naïve patients resulted in high rates of virological, biochemical, and histological response, with minimal resistance.
评估恩替卡韦在初治慢性乙型肝炎患者中的长期疗效。
167 例接受恩替卡韦 0.01mg、0.1mg 或 0.5mg 治疗 24-52 周的 II 期研究患者进入 ETV-060 扩展研究，并接受恩替卡韦 0.5mg 每日治疗。在有可用样本的患者中评估应答情况。
在 ETV-060 中 96 周（总恩替卡韦治疗时间 120-148 周）后，88%（127/144）的患者 HBV-DNA<400 拷贝/ml；基线 ALT 异常的 128/142 例患者中 90.1%（ALT 为正常值上限的 1 倍）；基线 HBeAg(+)的 121 例患者中 26%（32/121）实现 HBe 血清学转换。66 例患者的亚组从 II 期基线开始接受恩替卡韦 0.5mg（批准剂量）：在 ETV-060 的第 96 周，83%（48/58）的患者 HBV-DNA<400 拷贝/ml，88%（52/59）的患者 ALT 为正常值上限的 1 倍，20%（10/49）实现 HBe 血清学转换。66 例患者中有 21 例有配对的基线和治疗期间的肝活检：21 例（21/21）患者的组织学改善率为 100%，21 例（21/21）患者的纤维化改善率分别为 57%，经过 3 年的治疗。所有患者的耐药累积概率为 3.3%，0.5mg 亚组为 1.7%。
初治患者长期应用恩替卡韦可获得高病毒学、生化学和组织学应答率，耐药率低。
