摘要：
Objective To investigate the efficacy of pegylated interferon alpha-2a (peg-IFN-α-2a) temporary add-on therapy during entecavir (ETV) treatment by comparing with ETV monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB),and to discuss the differences of efficacy between these two strategies.Methods Sixty-one HBeAg-positive patients with CHB were administered with ETV at initial 24 weeks and were assigned randomly to either receive a 24 weeks addition of peg-IFN-α-2a 180 μg weekly or continue on ETV 0.5 mg daily alone for 24 weeks.Response was assessed at week 48 post-treatment and defined as HBeAg loss with hepatitis B virus (HBV) DNA ＜200 IU/mL.Then the responders were asked to discontinue the antiviral treatment at week 72.Non-responders continue the antiviral treatment with ETV until 96 weeks.All included patients were followed up until 96 weeks from the baseline.Quantitative data were compared using t test or rank sum test.Categorical data were analyzed using x2 test.Results Fifty-nine patients accomplished 96 weeks study,29 with ETV alone and 30 with add-on peg-IFN-α-2a.Response at week 48 was achieved in 20.0％ (6 cases) of patients treated with add-on peg-IFN-α-2a,compared to 13.8％ (4 cases) of patients treated with ETV alone (x2 =0.083,P=0.773) ; while the response rates at week 96 was 33.3％ (10 cases) in add-on peg-IFN-α 2a group and 20.7％ (6 cases) in ETV monotherapy group (x2 =1.193,P=0.275).At week 96,the declines of HBsAg between two regimens were 1.05 lg IU/mL and 0.34 lg IU/mL,respectively (Z=-2.972,P=0.003).The analyses on HBeAg levels showed that there were no significant difference between two regimens at week 24,week 48,week 72 and week 96 (all P＞0.05).Serum levels of HBsAg and HBeAg at baseline,week 12 and week 24 were significantly lower in HBeAg clearance group than non-clearance group (all P＜0.01).Conclusions A short term add-on of peg-IFN-α-2a during ETV treatment increases HBsAg decline.Baseline HBsAg level and on-treatment HBsAg and HBeAg declines may predict the virological response of CHB patients.%目的 研究以恩替卡韦(ETV)为基础,短程联用聚乙二醇干扰素-α-2a(peg-IFN-α-2a)抗病毒治疗HBeAg阳性CHB的临床疗效,并与ETV单药治疗比较,探讨两种治疗方法在临床疗效中的差异.方法 61例HBeAg阳性CHB患者在初始予以ETV 0.5 mg/d口服24周后,随机分为联合治疗组和单药治疗组,分别加用peg-IFN-α-2a 180 μg/周治疗24周或单药ETV 0.5 mg/d治疗24周.48周评估疗效.应答定义为HBeAg消失伴HBV DNA＜200 IU/mL.有应答者继续使用ETV巩固治疗至72周后停止抗病毒治疗.无应答者继续ETV治疗至96周,所有患者均随访至96周.计量资料比较采用t检验和秩和检验,计数资料比较采用x2检验和四格表法.结果 完成96周随访的患者共59例,ETV单药治疗组29例,联合治疗组30例.48周时联合治疗组和单药治疗组病毒学应答分别占20.0％(6例)和13.8％(4例;x2=0.083,P=0.773),96周时分别占33.3％(10例)和20.7％(6例;x2=1.193,P=0.275).联合治疗组和单药治疗组在96周时HBsAg分别降低1.05、0.34 lg IU/mL(Z=-2.972,P=0.003);各观察时间点HBeAg在两组间差异均无统计学意义(均P＞0.05).HBeAg清除组在基线、12周和24周的HBsAg和HBeAg水平均低于HBeAg未清除组(均P＜0.01).结论 接受ETV治疗的患者,短程联用peg-IFN-α-2a能显著降低患者血清HBsAg水平.CHB患者抗病毒治疗前HBsAg水平,以及第12周和24周的HBsAg和HBeAg水平或可作为患者发生病毒学应答的预测指标.
