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(5 S/CO＜ HBeAg＜ 50 S/CO),且血清HBsAg定量＜5000 IU/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HBV DNA、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x2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HBV DNA和HBV cccDNA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(x2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HBV DNA和HBV cccDNA载量分别为(6.93±0.52) lg IU/mg和(5.63±0.54)1g 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HBV DNA载量为(7.09±0.43)1g 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HBV cccDNA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,加用聚乙二醇干扰素α-2a,有利于提高血清HBeAg的阴转率和血清学转换率,并加速肝组织HBV DNA、HBV cccDNA的清除.

abstractsObjective 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 e antigen (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-a-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 (x2 =5.38 and 4.69,respectively,both P＜0.05).HBeAg titers of both groups were significantly lower than those of baseline (t=8.43 and 8.50,respectively,both P＜0.05).The HBeAg titer of combination therapy group was lower than that of monotherapy group (t=5.60,P＜ 0.01).HBV DNA and HBV cccDNA in liver tissue of combination therapy group was (6.934±0.52) lg IU/mg and (5.63±0.54) lg IU/mg post-treatment,respectively,which were both lower than baseline (t＝7.12.6.67,respectively,both P＜0.01).HBV DNA in liver tissue of monotherapy group was (7.09＝0.43) lg IU/mg post-treatment,which was lower than baseline (t=2.67,P=0.02).After treatment,HBV cccDNA in liver tissue of combination therapy group was lower than that of monotherapy group (t =2.87,P=0.00).Conclusions Compared with ADV monotherapy,sequential add-on of PEGIFN-a-2a in combination with ADV can achieve higher serum HBeAg loss rate and seroconversion rate and facilitate the clearance of hepatic HBV DNA and HBV cccDNA in CHB patients with low HBeAg titer after long-term ADV monotherapy.