阿德福韦酯序贯聚乙二醇干扰素α-2a治疗HBeAg低效价慢性乙型肝炎患者的疗效  

Efficacy of sequential add-on pegylated interferon α-2a in combination with adefovir dipivoxil in chronic hepatitis B patients with low serum HBeAg titer

作　　者：房建婷[1] 纪永健[2] 李菲菲[1] 孙希珍[1] 任万华[1] 

机构地区：[1]山东大学附属省立医院感染科,济南250021 [2]德州市人民医院感染科

出　　处：《中华传染病杂志》2013年第10期608-612,共5页Chinese Journal of Infectious Diseases

基　　金：山东省科技攻关课题（2010GSFl0271）

摘　　要：目的探讨阿德福韦酯长期单药治疗后仍处于HBeAg低效价的慢性乙型肝炎患者，加用聚乙二醇干扰素α-2a治疗48周的疗效。方法本研究为随机、开放、前瞻性的临床试验。将阿德福韦酯单药治疗72～144周仍处于低HBeAg效价（5S／CO〈HBeAg〈50S／CO），且血清HBsAg定量〈5000IU／mL的患者按随机数字表法分为单药组和加药组，单药组继续阿德福韦酯单药治疗48周，加药组加用聚乙二醇干扰素α-2a治疗48周，比较两组治疗前后血清HBeAg效价下降程度、阴转率、血清学转换率和肝组织HBVDNA、HBV共价闭合环状脱氧核糖核酸（cccDNA）载量的下降程度，对两种治疗方案进行疗效评估。患者治疗前后比较采用配对样本t检验，组间比较采用独立样本t检验，组间率的比较采用X^2检验。结果共纳入55例慢性乙型肝炎患者，单药组27例，加药组28例，两组患者年龄分布、性别比例、ALT、AST、TBil、血清HBeAg和HBsAg、肝组织HBVDNA和HBVcccDNA载量在基线水平比较差异均无统计学意义（均P〉0．05）。治疗48周后，单药组完成试验25例，加药组26例。加药组HBeAg阴转率、血清转换率均高于单药组（X^2值分别为5．38、4．69，均P〈0．05）。两组HBeAg效价均较基线值下降（t值分别为8．43和8．50，均P〈0．01）；加药组HBeAg效价低于单药组（t=5．60，P〈0．01）。加药组治疗48周HBVDNA和HBVcccDNA载量分别为（6．93±0．52）lgIU／mg和（5．63±0．54）lg IU／mg，与基线值比较差异均有统计学意义（t值分别=7．12和6．67，均P〈0．01）。单药组治疗48周HBVDNA载量为（7．09±0．43）lg IU／mg，与基线值比较差异有统计学意义（t=2．67，P=0．02）；治疗后48周，加药组与单药组HBVcccDNA载量比较差异有统计学意义（t=2．87，P=0．00）。结论经阿德福韦酯长期治疗后仍处于HBeAg低效价的慢性乙型肝炎患者，加用聚乙二醇干扰Objective To investigate the efficacy of sequential add-on of pegylated interferon α-2a （PEGIFN-α-2a） for 48 weeks in chronic hepatitis B （CHB） patients with low serum hepatitis B eantigen （HBeAg） titer after long-term adefovir dipivoxil （ADV） monotherapy. Methods This was a randomized, open and prospective clinical trial. Patients who had been treated with ADV for 72 to 144 weeks, with undetectable serum hepatitis B virus （HBV） DNA level, low HBeAg titer （5 S/CO〈 HBeAg〈50 S/CO） and serum hepatitis B surface antigen （HBsAg） 〈5000 IU/mL were included. The patients were categorized into ADV monotherapy group and ADV plus PEGIFN-α-2a combination therapy group by random number table. Patients in ADV group continued ADV monotherapy and patients in combination therapy group added PEGIFN-α-2a to ADV for 48 weeks. After the treatment, efficacy of the two therapies were assessed by comparing the reduction of serum HBeAg reduction, HBeAg loss rate, HBeAg seroconversion rate, and reduction of intrahepatic HBV DNA and HBV covalently closed circular DNA （cccDNA）. Pre- and post-treatment results were compared by paired samples t test. Comparison between groups was performed using indepedent samples t test. Comparison of rates between groups was performed using X2 test. Results The trial enrolled 55 CHB patients, and there were 27 patients in ADV monotherapy group, 28 patients in combination therapy group. Baseline characteristics including age distribution, sex ratio, alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, total bilirubin （TBil）, serum HBeAg and HBsAg, hepatic HBV DNA and HBV cccDNA were all comparable （all P〉0. 05）. Twenty-five patients in ADV monotherapy group and 26 patients in combination therapy group completed 48 weeks treatment. HBeAg loss rates and seroconversion rates of combination therapy group were higher than those of ADV monotherapy group （X^2 = 5. 38 and 4. 69, respectively, both P〈0. 05）. HBeAg titers of both groups wer

关 键 词：肝炎 乙型 慢性 腺嘌呤 干扰素Α-2A 聚乙烯二醇类 DNA 环状 病毒 肝炎E抗原 

分 类 号：R512.62[医药卫生—内科学]