摘要目的 评估序贯聚乙二醇干扰素(Peg-IFN)α-2a治疗恩替卡韦经治HBeAg阳性慢性乙型肝炎的疗效与安全性.方法 57例恩替卡韦治疗96周达到HBV DNA＜500拷贝/ml且0.227PEIU/ml＜HBeAg≤50.000 PEIU/ml的HBeAg阳性慢性乙型肝炎患者,27例接受ETV与PegIFN α-2a联合治疗12周后改为Peg-IFN α-2a单药治疗至48周(试验组),30例继续接受恩替卡韦治疗48周(对照组),分别在治疗的24、48周进行生物化学、病毒学、血清学评估.统计学处理用t检验或x2检验.结果 试验组与对照组基线ALT、HBsAg、HBeAg水平有可比性.治疗48周,试验组HBeAg阴转率与HBeAg血清学转换率分别为40.7％和37.0％,与对照组的16.7％和13.3％相比,差异有统计学意义(x2值分别为4.079和5.11,P值均＜0.05).试验组HBsAg清除率和HBV DNA反弹率分别7.4％与11.1％,对照组无HBsAg清除和HBV DNA反弹(x2值分别为2.307 和3.519,P值均＞0.05).治疗48周,试验组HBsAg水平明显低于对照组[(2866.0±2580.4)IU/ml对比(4335.8±2650.0) IU/ml,t=5.11,P＜0.05]. 结论 恩替卡韦经治的HBeAg阳性慢性乙型肝炎患者,序贯Peg-IFNα-2a治疗有助于实现HBeAg血清转换和HBsAg定量下降.

abstractsObjective To investigate the efficacy and safety of peginterferon alfa-2a (Peg-IFNα-2a) therapy for treating chronic hepatitis B (CHB) in patients who failed to achieve a satisfactory end point with entecavir (ETV) treatment.Methods Fifty-seven CHB patients with positivity for hepatitis B e antigen (HBeAg) who had completed a standard ETV monotherapy course,of at least 96 weeks,and who had achieved a virological response (defined as HBV DNA ＜ 500 copies/ml) but without HBeAg seroconversion (defined as 0.227 PEI U/ml ＜ HBeAg ≤ 50 PEI U/ml) were enrolled in the study.The patients were randomly assigned to receive a 48-week treatment with Peg-IFNα-2a (experimental group,n =27) or continued ETV therapy (control group,n =30).Serum samples were collected from all patients for assessment of biochemical,virological and serological responses to treatment.Inter-group differences were statistically evaluated by t-test or Chi-squared test.Results The baseline levels of alanine aminotransferase,hepatitis B surface antigen (HBsAg),and HBeAg were similar between the patients comprising the experimental and controls groups.At treatment week 48,the experimental group showed significantly higher rates of HBeAg clearance (Peg-IFNα-2a:40.7％ vs.ETV:16.7％,x2 =4.079,P ＜ 0.05)and seroconversion (37.0％ vs.13.3％,x2 =5.110,P ＜ 0.05).The experimental group also showed higher ates of HBsAg clearance (7.4％ vs.0％) and HBV DNA relapse (11.1％ vs.0％),but the differences did not reach statistical significance (x2 =2.307 and 3.519,both P ＞ 0.05).However,the level of HBsAg was significantly lower in the experimental group (2866.0 + 2580.4 vs.4335.8 + 2650.0 IU/ml,t =5.11,P ＜0.05).Conclusion HBeAg-positive CHB paitents with unsatisfactory response to initial ETV monotherapy achieved HBeAg seroconversion and clearance following sequential Peg-IFN a-2a treatment.