阿德福韦酯联合干扰素α治疗HBeAg阳性慢性乙型肝炎的系统评价

Systematic review on adefovir dipivoxil plus interferon α for the treatment of HBeAg-positive chronic hepatitis B

目的系统性评价干扰素α联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性。方法采用Cochrane系统评价方法,检索Cochrane图书馆临床对照试验数据库、PubMed、EMbase、CBM、CNKI、中文科技期刊数据库(VIP)和万方数据库等电子资料库。由2名评价者共同评价纳入研究的质量,对同质研究进行Meta分析。结果纳入9个研究,共653例慢性乙型肝炎患者。纳入文献均未描述具体随机方法,未描述分配隐藏方法,未实施盲法。按测量指标和干预措施进行亚组分析:①与单用阿德福韦酯比较,治疗24周时联合用药在HBeAg血清学转换率方面与对照组差异无统计学意义,治疗48周时联合用药在ALT复常率、HBVDNA低于检测下限的比率、HBeAg血清学转换率方面优于对照组,差异有统计学意义,但HBsAg转阴率与对照组差异无统计学意义;②与单用干扰素α比较,治疗24、48周时联合用药在ALT复常率、HBVDNA低于检测下限的比率、HBeAg血清学转换率方面优于对照组,但随访48周时与对照组差异无统计学意义,HBsAg转阴率与对照组差异无统计学意义;③与干扰素α联合拉米夫定组比较,在HBVDNA低于检测下限的比率、HBeAg血清学转换率、HBsAg阴转率方面与对照组差异无统计学意义。结论现有研究显示,干扰素α联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎对ALT、病毒学指标、病毒学应答的改善较单药治疗有效,且不增加严重不良反应的发生率。但本系统评价所纳入的文献多为较低质量的小样本研究,且用药时间不同,因此无法进行总体的效应合并分析,尚需更大量的文献支持。

Objective To evaluate the effect and safety of adefovir dipivoxil plus interferon α for HBeAg-positive chronic hepatitis B. Methods The Cochrane Database of Controlled Trials Register （CCTR）, PubMed, EMBASE, the Chinese Biomedical Database （CBM）, CNKI, Chinese Scientific and Technological Journal Database （VIP database） and Wanfang Database were searched. Quality assessment and data extraαion were conduαed by two reviewers independently and disagreements, if any, were resolved by discussion. Meta-analysis were performed for homogeneous studies. Results Total of 9 studies involved and 653 patients met the inclusion criteria. None of the trials enforced allocation concealment and none performed blinding. Subgroup analysis based on the outcome measures and interventions were carried out. Compared with ADV monotherapy, there was no significant differences in terms of HBeAg, seroconversion rate when the treatment course was 24 weeks. Treatment group was significantly effeαive in ALT normalization, HBV DNA and HBeAg clearance when the treatment course was longer than 48 weeks. But there was no significant differences on HBsAg seroconversion rate improvement. Compared with interferon α monotherapy, treatment group was significantly effeαive in ALT normalization, HBV DNA and HBeAg clearance when the treatment course was 24 or 48 weeks, but there were no significant differences when following up for 48 weeks. Compared with LAM plus interferon α combination therapy, there were no significant differences in terms of ALT normalization, HBV DNA, HBeAg and HBsAg clearance. Conclusions ADV plus interferon α combination therapy might be effeαive in ALT normalization, HBV DNA clearance and viral seroconversion, without any serious adverse effeαs. However, the overall effeαs cannot be pooled for analysis and more evidences are needed.