Objective To identify and validate the potential parameters to predict HBeAg persistence in patients with virological response under long-term nucleoside analogues treatment. Methods HBeAg-positive patients with sustained virological response under long-term nucleoside analogues treatment were analyzed. Variables at baseline and HBeAg titers after first onset of undetectable viremia (FOUV)were adopted for further analysis. Results In study cohort (n= 44,lamivudine therapy),HBeAg levels in 6 months after FOUV could predict HBeAg persistence (AUROC= 0.874,P= 0.023). 64.0% patients with HBeAg titers ≥ 10.0 s/co at the time point failed to clear HBeAg [follow-up treatment lasted 30 (24-33)months]. This proportion was 88.0% in test cohort [n= 171,entecavir therapy, virological response maintenance was 1 5 (6-5 1 )months ]. Conclusions HBeAg could persist in most patients with HBeAg levels ≥ 10.0 s/co in 6 months after FOUV although virological responses are maintained under long-term nucleoside analogues therapy.%目的：寻找并验证长期核苷类药物治疗获得病毒学应答慢性乙型肝炎患者 HBeAg 持续阳性的预测指标。方法以治疗基线 HBeAg阳性、长期核苷类药物治疗获得维持病毒学应答的慢性乙型肝炎患者为对象，分析治疗基线指标及首次病毒学应答后的 HBeAg效价对 HBeAg 持续阳性的预测价值。结果学习队列（n＝44，拉米夫定治疗）的患者首次病毒学应答后6个月的 HBeAg 效价可预测 HBeAg 持续阳性（ROC 曲线下面积＝0．875，P＝0．023）：HBeAg≥10．0 s/co（雅培Architect i2000检测）者不能清除 HBeAg的比例为64．0％（后续治疗时间24～33个月，中位数30）。验证队列（n＝171，恩替卡韦治疗）中，病毒学应答后6个月 HBeAg≥10．0 s/co 的患者88．0％持续 HBeAg 阳性，维持病毒学应答时间为15（6～51）个月。结论长期核苷类药物治疗 HBeAg阳性慢性乙型肝炎时虽可维持病毒学应答，但病毒学应答后6个月 HBeAg≥10．0 s/co的患者难以清除 HBeAg。
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