Suzuki Fumitaka, Toyoda Joji, Katano Yoshiaki, Sata Michio, Moriyama Mitsuhiko, Imazeki Fumio, Kage Masayoshi, Seriu Taku, Omata Masao, Kumada Hiromitsu
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
J Gastroenterol Hepatol. 2008 Sep;23(9):1320-6. doi: 10.1111/j.1440-1746.2008.05455.x. Epub 2008 Jun 28.
Entecavir is a potent inhibitor of both wild-type and lamivudine-resistant hepatitis B virus (HBV) with proven clinical efficacy. We conducted a randomized, double-blind, multicenter study in Japan (ETV-052) evaluating the efficacy and safety of two doses of entecavir in adult patients with lamivudine-refractory chronic hepatitis B infection.
Eighty-four patients with chronic hepatitis B who were refractory to lamivudine therapy were switched from lamivudine to daily oral doses of 0.5 mg entecavir (41 patients) or 1 mg entecavir (43 patients) for 52 weeks.
The proportions of patients achieving the primary end-point (>or=2 log(10) reduction in HBV-DNA from baseline by polymerase chain reaction assay or undetectable HBV-DNA levels [<400 copies/mL] at week 48) were 90% and 93% for entecavir 0.5 mg and 1 mg, respectively, with 33% of patients in each dosing group achieving <400 copies/mL. The mean reduction in HBV-DNA from baseline was 3.58 and 3.75 log(10) copies/mL for entecavir 0.5 mg and 1 mg, respectively. High proportions of patients achieved alanine aminotransferase normalization at week 48 (0.5 mg 86%, 1 mg 78%). Histological improvement was observed in most patients (0.5 mg 52%, 1 mg 60%). Virological breakthrough (increase in HBV-DNA of >or=1 log(10) copies/mL from nadir) was observed in one patient but was not associated with selection of entecavir-associated resistance substitutions. Entecavir was well tolerated, with no patients discontinuing study drug due to adverse events.
These findings indicate that entecavir is safe and effective for the treatment of Japanese adults with lamivudine-refractory chronic hepatitis B.
恩替卡韦是一种对野生型及拉米夫定耐药的乙型肝炎病毒（HBV）均有强效抑制作用的药物，临床疗效已得到证实。我们在日本开展了一项随机、双盲、多中心研究（ETV - 052），以评估两种剂量的恩替卡韦对拉米夫定治疗无效的成年慢性乙型肝炎感染患者的疗效和安全性。
84例对拉米夫定治疗无效的慢性乙型肝炎患者从拉米夫定换用恩替卡韦，每日口服0.5毫克（41例患者）或1毫克（43例患者），疗程52周。
达到主要终点（通过聚合酶链反应检测，HBV - DNA水平较基线降低≥2 log₁₀，或在第48周时HBV - DNA水平不可检测[<400拷贝/毫升]）的患者比例，恩替卡韦0.5毫克组和1毫克组分别为90%和93%，每个剂量组均有33%的患者HBV - DNA水平<400拷贝/毫升。恩替卡韦0.5毫克组和1毫克组的HBV - DNA较基线的平均降低值分别为3.58和3.75 log₁₀拷贝/毫升。在第48周时，高比例患者的丙氨酸氨基转移酶恢复正常（0.5毫克组86%，1毫克组78%）。大多数患者出现组织学改善（0.5毫克组52%，1毫克组60%）。在1例患者中观察到病毒学突破（HBV - DNA较最低点升高≥1 log₁₀拷贝/毫升），但与恩替卡韦相关耐药替代位点的选择无关。恩替卡韦耐受性良好，无患者因不良事件而停用研究药物。
这些研究结果表明，恩替卡韦对治疗拉米夫定治疗无效的日本成年慢性乙型肝炎患者安全有效。
