摘要目的 评价聚乙二醇干扰素α-2a(Peg IFNα-2a)联合阿德福韦酯(ADV)治疗非活动性HBsAg携带者(IHC)的有效性及安全性.方法 本研究为单中心、前瞻性、开放性临床研究.IHC按照个人意愿分为治疗组和对照组.治疗组中HBV DNA<20 IU/mL者仅予Peg IFNα-2a,≥20~<2 000 IU/mL者予Peg IFNα-2a联合ADV,疗程96周.但若患者获得HBsAg血清学转换后巩固治疗24周,总疗程虽不到96周,也可提前停药.两组间连续变量比较采用t检验,计数资料采用χ2 检验或Fisher确切概率法,对影响HBsAg清除的相关因素采用单因素和多因素Logistic回归分析.结果 共入组184例IHC患者,治疗组112例,对照组72例.治疗组治疗48周时HBsAg清除率及血清学转换率分别为30.8%(32/104)、26.0%(27/104),96周时上升至45.2%(47/104)和38.5%(40/104);对照组治疗48及96周时HBsAg清除率均为1.5%(1/68),无HBsAg血清学转换者;治疗组HBsAg清除率显著高于对照组(χ2=39.066,P<0.01).基线(OR=2.313,95%CI:1.258~4.251,P=0.007)、治疗12周(OR=3.159,95%CI:1.826~5.466,P<0.01)及24周(OR=3.347,95%CI:2.050~5.465,P<0.01)的HBsAg定量,治疗12周(OR=5.343,95%CI:2.085~13.689,P<0.01)及24周(OR=4.855,95%CI:2.380~9.902,P<0.01)HBsAg下降幅度,治疗12周ALT是否升高(OR=3.520,95%CI:1.369~9.052,P=0.009),均是HBsAg清除的独立预测因素.结论 Peg IFNα-2a治疗IHC可获得较高HBsAg清除率或血清学转换率,而且安全性良好.治疗12、24周HBsAg下降显著,同时伴有12周ALT升高,预示可获得较高的HBsAg清除率.

abstractsObjective To evaluate the feasibility and safety profile of pegylated-interferonα-2a (Peg IFNα-2a) combined with adefovir dipivoxil (ADV) in inactive hepatitis B surface antigen (HBsAg) carriers (IHC).Methods This was a single center, prospective and open-label study.IHC were divided into therapeutic group (T, 112 subjects) and control group (C, 72 subjects) according to personal willingness.Patients with hepatitis B virus (HBV) DNA<20 IU/mL were treated with Peg IFNα-2a monotherapy, and those with HBV DNA ≥20-<2 000 IU/mL were treated with Peg IFNα-2a combined with ADV.Total therapy duration was 96 weeks.For patients who achieved HBsAg seroconversion and continued consolidation treatment for 24 weeks, the treatment duration could be less than 96 weeks.t test was used for continuous variable comparison between the two groups, while chi-square test or Fisher′s exact probability method was used for counting data analysis.The related factors affecting HBsAg clearance was analyzed by univariate or multivariate logistic regression analysis.Results A total of 194 patients were enrolled with 112 in therapeutic group and 72 in control group.The HBsAg clearance rate and seroconversion rate at week 48 in therapeutic group were 30.8% (32/104) and 26.0% (27/104), respectively.The rates at week 96 increased to 45.2% (47/104) and 38.5% (40/104), respectively.The HBsAg clearance rates at weeks 48 and 96 in control group were both 1.5% (1/68).HBsAg seroconversion was not achieved in control group.The HBsAg clearance rate in treatment group was significantly higher than that in control group (χ2=39.066, P<0.01).The quantitative HBsAg levels at baseline (OR=2.313, 95%CI: 1.258-4.251, P=0.007), week 12 (OR=3.159, 95%CI: 1.826-5.466, P<0.01) and week 24 (OR=3.347, 95%CI: 2.050-5.465, P<0.01), the decline of HBsAg at week 12 (OR=5.343, 95%CI: 2.085-13.689, P<0.01), and week 24 (OR=4.855, 95%CI: 2.380-9.902, P<0.01), and alanine transaminase (ALT) elevation at week 12 (OR=3.520, 95%CI: 1.369-9.052, P=0.009) were independent predictors for HBsAg clearance.Conclusions Peg IFNα-2a-based treatment for IHC could achieve higher HBsAg clearance rate and seroconversion rate, and has a safety profile.Decline of HBsAg at week 12 and week 24 with ALT elevation at week 12 could predict a higher HBsAg clearance rate.