核苷(酸)类似物序贯/序贯联合聚乙二醇干扰素治疗HBeAg阳性慢性乙型肝炎的Meta分析

Meta analysis on nucleo(s)tide analogues sequential/sequential combined with pegylated interferon for the therapy of HBeAgpositive chronic hepatitis B

摘要:

目的系统评价核苷(酸)类似物(NAs)序贯/序贯联合聚乙二醇干扰素(PegIFN)治疗HBeAg阳性慢性乙型肝炎(CHB)的有效性及安全性。方法检索建库至2017年3月25日PubMed、Cochrane Library、Embase、中国期刊全文数据库、万方数据知识服务平台、中文科技期刊全文数据库，纳入NAs抗病毒治疗产生病毒学应答后，序贯/序贯联合PegIFN治疗CHB患者的随机对照试验(RCT)，采用RevMan 5.3软件进行Meta分析，比较治疗结束时HBeAg血清学转换率及HBsAg阴转率。 结果最终纳入9个研究，NAs序贯PegIFN研究4个，NAs序贯联合PegIFN研究5个。治疗结束时，与单用NAs相比，NAs序贯/序贯联合PegIFN治疗可提高HBeAg血清学转换率(31.2％ vs 11.7％，OR=3.69，95％CI为2.43～5.60，P＜0.01)，提高HBsAg阴转率(11.5％ vs 0.5％，OR=9.31，95％CI为2.72～31.89，P＜0.01)。亚组分析结果显示，NAs序贯PegIFN治疗组的HBeAg血清学转换率高于对照组［25.3％(42/166) vs 10.0％(17/170)，OR=3.1，95％CI为1.66～5.79，P＜0.01］；NAs序贯联合PegIFN治疗组的HBeAg血清学转换率高于对照组［36.8％(63/171) vs 13.5％(23/171)，OR=4.24，95％CI为2.41～7.46，P＜0.01］。序贯/序贯联合治疗组不良反应多见，大多数可耐受或对症处理后好转。结论HBeAg阳性CHB抗病毒治疗中，应用NAs产生病毒学应答后，序贯/序贯联合PegIFN治疗48周可提高HBeAg血清学转换率及HBsAg阴转率。

Abstract:

ObjectiveTo systematically evaluate the efficacy and safety of nucleo(s)tide analogues (NAs) sequential/NAs sequential combined with pegylated interferon (PegIFN) for the treatment of HBeAgpositive chronic hepatitis B（CHB）. MethodsPubMed, Cochrane Library, Embase, and Chinese Medical databases (CNKI, Wanfang and VIP) from database establishment to March 25, 2017 were retrieved, randomized controlled trials of NAs sequential/sequential combined with PegIFN for the treatment of CHB after application of NAs to achieve virologic response were included in study, Meta analysis was performed by RevMan 5.3 software, HBeAg seroconversion rate and HBsAg negative conversion rate at the end of treatment were compared. ResultsNine studies were eventually included, 4 were about NAs sequential PegIFN,5 about NAs sequential combined with PegIFN. At the end of treatment, compared with using NAs monotherapy for antiviral treatment, NAs sequential/sequential combined with PegIFN therapy can improve HBeAg seroconversion rate(31.2％ vs 11.7％；OR, 3.69 ［95％CI, 2.43-5.60］；P＜0.01) and HBsAg negative conversion rate(11.5％ vs 0.5％；OR, 9.31［95％CI, 2.72-31.89］；P＜0.01). According to the results of subgroup analysis, HBeAg seroconversion rate in NAs sequential PegIFN therapy group was higher than control group (25.3％［42/166］ vs 10.0％［17/170］; OR,3.1［95％CI, 1.66-5.79］；P＜0.01)；HBeAg seroconversion rate in NAs sequential combined with PegIFN therapy was higher than control group (36.8％［63/171］ vs 13.5％［23/171］；OR,4.24［95％CI, 2.41-7.46］；P＜0.01). Sequential/sequential combination therapy showed more adverse reaction, most of which can be tolerated or improved after symptomatic treatment. ConclusionFor the treatment of HBeAgpositive CHB, after application of NAs to achieve virologic response, NAs sequential/sequential combined with PegIFN therapy for 48 weeks can significantly increase HBeAg seroconversion rate and HBsAg negative conversion rate.