【摘要】 目的 采用高灵敏度实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction,qPCR）技术评估恩替卡韦（entecavir, ETV）初治慢性乙型肝炎（chronic hepatitis B,CHB）患者低病毒血症（low-level viremia, LLV）的发生率及危险因素。方法 开展全国多中心横断面研究，研究采用分层整群抽样方式，覆盖全国七大地理区域中14个省市、39家三级甲等具有代表性的肝病或传染病医院。纳入在2020年1月1日至4月30日期间就诊的接受ETV治疗24～48周且按当地医院标准乙肝病毒脱氧核糖核酸（hepatitis B virus deoxyribonucleic acid,HBV DNA）转阴的CHB患者，本研究使用检测下限为10 IU/mL的qPCR重新检测血清HBV DNA水平。LLV定义为HBV DNA处于10～2 000 IU/mL。采用多因素logistic回归分析独立预测因素。结果 在1 000例常规检测“转阴”患者中，41.8%(418/1 000)存在LLV。多因素分析确认：年龄<45岁（OR=2.236, 95%CI:1.701～2.940, P<0.01）、乙型肝炎病毒e抗原（hepatitis B virus early antigen,HBeAg）阳性（OR=3.821,95%CI:2.829～5.161,P<0.01）为LLV的独立危险因素。延长ETV疗程仅显示微弱保护效应（OR=0.980,P=0.029,95%CI:0.963～0.998），但该效应在HBeAg阳性亚组消失（P=0.068）。结论 年龄<45岁和HBeAg阳性是发生LLV的关键风险因素。ETV延长治疗对HBeAg阳性患者保护作用有限，提示针对高危人群应早期更换治疗方案以及初始治疗时需慎重选择ETV。更多还原

【Abstract】 Objective To assess the prevalence and risk factors of low-level viremia(LLV) in chronic hepatitis B(CHB) patients receiving initial entecavir(ETV) therapy using high-sensitivity quantitative real-time polymerase chain reaction(qPCR). Methods A national multicenter cross-sectional study was conducted. The study adopted stratified cluster sampling and covered 14 provinces and municipalities in seven major geographical regions across the country, involving 39 representative tertiary grade-A hospitals specializing in liver diseases or infectious diseases. Patients with chronic hepatitis B(CHB) who received entecavir(ETV) treatment for 24 to 48 weeks and achieved hepatitis B virus deoxyribonucleic acid(HBV DNA) negativity according to local hospital standards during the period from January 1 to April 30, 2020 were included. Serum HBV DNA levels were retested by qPCR with a limit of detection of 10 IU/mL. LLV was defined as HBV DNA of 10-2 000 IU/mL. Multivariate logistic regression analysis was performed to identify independent risk factors. Results Among 1 000 patients with undetectable HBV DNA on routine testing, 41. 8%(418/1 000) had LLV. Multivariate analysis confirmed that age < 45 years(OR=2. 236, 95%CI:1. 701-2. 940, P<0. 01) and HBeAg positivity(OR=3. 821, 95% CI:2. 829-5. 161, P<0. 01) were independent risk factors for LLV. Prolonged ETV treatment showed only a weak protective effect(OR=0. 980, 95%CI:0. 963-0. 998, P=0. 029), whereas this effect was absent in the HBeAg-positive subgroup(P=0. 068). Conclusion Age < 45 years and HBeAg positivity are key risk factors for the occurrence of LLV. Prolonged ETV therapy offers limited protection in HBeAg-positive patients, suggesting that treatment should be modified early for highrisk populations and that ETV should be carefully selected for initial therapy.更多还原