α干扰素治疗HBeAg阳性慢性乙型肝炎疗效的荟萃分析

目的评价α干扰素治疗HBeAg阳性慢性乙肝病毒感染儿童的长期疗效及安全性。方法检索PubMed和CHKD期刊全文数据库,并追查所有纳入研究的参考文献,进行荟萃分析。纳入用英文或中文发表的比较α干扰素与非抗病毒药物（安慰剂或空白对照）治疗HBeAg阳性慢性乙肝病毒感染儿童的随机对照试验。结果共纳入10个随机对照试验,包括542个HBsAg和HBeAg阳性的慢性乙型肝炎患儿。结果显示,随访6个月～2年,α干扰素组HBeAg转阴率高于对照组31．1％vs12．4％,OR3．17,95％CI（2．00,5．02）,P〈0．00001],HBV—DNA转阴率高于对照组33．9％vs16．2％,OR2．59,95％CI（1．70,3．96）,P〈0．0001],HBsAg转阴率高于对照组5．5％vs1．2％,OR3．44,95％CI（1．20,9．89）,P=0．02],丙氨酸氢基转移酶（ALT）复常率高于对照组43．0％vs27．7％,OR1．99,95％CI（1．16,3．42）,P=0．01],HBeAg血清学转换率高于对照组30．4％vs12．8％,OR2．90,95％CI（1．56,5．39）,P=0．0008],两组差异均有统计学意义,但HBsAg血清学转换率与对照组相比1．9％vs0,95％CI（0．42,18．13）,P=0．29],差异无统计学意义。结论对HBeAg阳性的慢性乙肝病毒感染患儿,α干扰素可能有使HBeAg转阴、HBV-DNA转阴、HBsAg转阴、ALT复常及HBeAg血清学转换的效应,但未能实现HBsAg血清学转换。受原研究质量和不同研究干预措施差异的影响,α干扰素的效应尚需更多高质量足够样本量的随机对照试验予以证实。

Effect of interferon-alpha treatment in children with hepatitis B e antigen-positive chronic hepatitis B virus infection: a meta-analysis of follow-up for six months to two years

OBJECTIVE: To assess the efficacy and safety of interferon-alpha (IFN-alpha) in children with Hepatitis B e antigen-positive chronic hepatitis B virus infection. METHODS: PubMed and Chinese Biomedical Database were searched from the beginning of operation of the databases to April 2006, and the references of eligible studies were manually screened. Randomized controlled trials (RCTs) published in the English and Chinese literature comparing interferon-alpha with non-antiviral interventions (placebo or no treatment) in children with hepatitis B e antigen-positive chronic hepatitis B virus infection were eligible for inclusion. Studies were included if patients were treated for at least 3 months and followed-up for at least 6 months after cessation of therapy. Two investigators independently assessed the quality and extracted the data. The methodological quality of trails was assessed by the Jadad-scale plus allocation concealment. Heterogeneity was examined by Chi-square test. Fixed effects model or random effects model were used to pool the data. Sensitivity analyses were used for the treatment course. RESULTS: Ten randomized controlled studies with a total of 542 children chronic HBV carriers who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were identified. It was found by the meta-analysis that, compared with the control, at the end of the follow-up period, IFN-alpha could still significantly clear HBeAg 31.1% vs. 12.4%, odds ratio (OR): 3.17, 95% CI (2.00, 5.02), P < 0.000 01], clear HBV-DNA 33.9% vs. 16.2%, OR: 2.59, 95% CI (1.70, 3.96), P < 0.0001], clear HBsAg 5.5% vs. 1.2%, OR: 3.44, 95% CI (1.20, 9.89), P = 0.02], normalize ALT 43.0% vs. 27.7%, OR: 1.99, 95% CI (1.16, 3.42), P = 0.01], and achieve HBeAg seroconversion 30.4% vs. 12.8%, OR: 2.90, 95% CI (1.56, 5.39), P = 0.0008], but was not effective in HBsAg seroconversion 1.9% vs. 0, 95% CI (0.42, 18.13), P = 0.29]. CONCLUSIONS: Interferon-alpha might be efficacious in clearance of HBeAg, HBV-DNA and HBsAg, normalization of ALT, and achievement of HBeAg seroconversion in children with chronic hepatitis B. Little evidence is available on HBsAg seroconversion. Further RCTs of high-quality and sufficient number of cases are needed for confirmation of the clinical efficacy of IFN-alpha in chronic hepatitis B in children.