Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
J Med Virol. 2015 Jun;87(6):999-1007. doi: 10.1002/jmv.24150. Epub 2015 Feb 24.
Entecavir (ETV) plus adefovir (ADV) combination therapy is one of the useful treatment option for the patients with chronic hepatitis B (CHB) who had failed on prior nucleos(t) ide analogue (NA) treatments. This study compared the efficacies of the combinations of ETV 0.5 mg plus ADV and ETV 1.0 mg plus ADV in patients who had failed on prior multiple NA treatments. This retrospective analysis included 148 consecutive patients with CHB infection in Korea (n = 37 with ETV 0.5 mg plus ADV and n = 111 with ETV 1.0 mg plus ADV). The virological and biochemical responses were compared between the two groups. The cumulative probability of viral suppression of ETV 0.5 mg plus ADV was not inferior to that of ETV 1.0 mg plus ADV (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.38-1.08; P = 0.094). The changes in serum HBV DNA level in the ETV 0.5 mg plus ADV group were not different between the two groups over 12 months. Moreover, no significant difference was observed in acquiring ETV-resistant variants between the two groups during the treatment (HR, 0.95; P = 0.953). This study suggests the proof-of-concept that the lower dose of NA in combination with other NA might be the theoretical option for rescue combination therapy in patients with CHB who had failed on prior multiple NA treatments in order to reduce systemic exposure and possible side effects of NA.
恩替卡韦（ETV）加阿德福韦（ADV）联合治疗是慢性乙型肝炎（CHB）患者的一种有效治疗选择，这些患者在先前的核苷（酸）类似物（NA）治疗中失败。本研究比较了 ETV 0.5mg 加 ADV 和 ETV 1.0mg 加 ADV 联合治疗方案在先前多种 NA 治疗失败的患者中的疗效。这项回顾性分析纳入了韩国 148 例连续的 CHB 感染患者（ETV 0.5mg 加 ADV 组 n=37，ETV 1.0mg 加 ADV 组 n=111）。比较了两组患者的病毒学和生化应答。ETV 0.5mg 加 ADV 的病毒抑制累积概率不劣于 ETV 1.0mg 加 ADV（风险比 [HR]，0.64；95%置信区间 [CI]，0.38-1.08；P=0.094）。在 12 个月内，ETV 0.5mg 加 ADV 组血清 HBV DNA 水平的变化在两组间无差异。此外，在治疗期间两组间未观察到获得 ETV 耐药变异的显著差异（HR，0.95；P=0.953）。本研究提示，在先前多种 NA 治疗失败的 CHB 患者中，联合其他 NA 使用低剂量 NA 进行挽救性联合治疗可能是一种理论选择，以降低 NA 的全身暴露和潜在的不良反应。
