Hepatol Int. 2010 Jul 8;4(3):594-600. doi: 10.1007/s12072-010-9185-3.
Current Japanese guidelines recommend that patients should be switched from lamivudine to entecavir when they meet certain criteria. This analysis examines the efficacy and safety of long-term entecavir therapy in patients who were switched to entecavir after 24 weeks' lamivudine therapy in Japanese studies ETV-047 and ETV-060.
The Phase II Japanese study ETV-047 assessed the efficacy of different entecavir doses when compared with lamivudine. A total of 33 Japanese patients who received lamivudine 100 mg daily in ETV-047 entered the open-label rollover study ETV-060 and subsequently received treatment with entecavir 0.5 mg daily. Hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroconversion, and resistance were evaluated among patients with available samples for up to 96 weeks. Safety was assessed throughout the treatment period.
After 96 weeks of entecavir therapy in ETV-060, 90% of patients achieved HBV DNA <400 copies/mL as compared to 21% of patients who completed 24 weeks of lamivudine therapy in ETV-047. Increasing proportions of patients achieved ALT normalization and HBeAg seroconversion following long-term entecavir treatment. No patients experienced virologic breakthrough, and substitutions associated with entecavir resistance were not observed in patients with detectable HBV DNA. Entecavir was well tolerated during long-term treatment.
Switching lamivudine-treated patients with chronic hepatitis B to entecavir results in increased virologic suppression with no evidence of resistance through 2 years of entecavir therapy. These findings support recommendations in the current Japanese treatment guidelines that stable lamivudine patients should be switched to entecavir.
目前日本指南建议，当患者符合某些标准时，应将拉米夫定转换为恩替卡韦。本分析检查了在日本 ETV-047 和 ETV-060 研究中，经过 24 周拉米夫定治疗后转换为恩替卡韦的患者长期接受恩替卡韦治疗的疗效和安全性。
日本的 II 期研究 ETV-047 评估了不同恩替卡韦剂量与拉米夫定相比的疗效。在 ETV-047 中每天接受拉米夫定 100mg 的 33 例日本患者进入开放标签扩展研究 ETV-060，并随后接受恩替卡韦 0.5mg 每日治疗。评估了有可用样本的患者在 96 周内的乙型肝炎病毒（HBV）DNA 抑制、丙氨酸氨基转移酶（ALT）正常化、乙型肝炎 e 抗原（HBeAg）血清学转换和耐药情况。在整个治疗期间评估安全性。
在 ETV-060 中接受恩替卡韦治疗 96 周后，90%的患者达到 HBV DNA <400 拷贝/ml，而在 ETV-047 中完成 24 周拉米夫定治疗的患者比例为 21%。随着长期恩替卡韦治疗，越来越多的患者实现 ALT 正常化和 HBeAg 血清学转换。没有患者出现病毒学突破，在可检测到 HBV DNA 的患者中未观察到与恩替卡韦耐药相关的替代。恩替卡韦在长期治疗中耐受性良好。
将慢性乙型肝炎的拉米夫定治疗患者转换为恩替卡韦可增加病毒学抑制，在 2 年的恩替卡韦治疗期间没有耐药证据。这些发现支持当前日本治疗指南的建议，即稳定的拉米夫定患者应转换为恩替卡韦。
