聚乙二醇干扰素α-2a联合阿德福韦治疗HBeAg阳性慢性乙型肝炎疗效系统评价

doi:10.3969/j.issn.1672-5069.2015.01.007

摘要/Abstract

摘要： 目的探讨聚乙二醇干扰素α-2a（Peg-IFNα-2a）联合阿德福韦（ADV）治疗HBeAg阳性慢性乙型肝炎（CHB）患者的临床疗效。方法通过检索2004年1月~2014年1月期间Pubmed、万方数据库（CECDB）、中文科技期刊数据库（VIP）、中国学术期刊全文数据库（CNKI）等有关Peg-IFNα-2a联合阿德福韦治疗HBeAg的CHB患者的随机对照试验（RCT）,对纳入文献的质量进行严格评价和资料提取,应用Stata/SE version 12.0软件对纳入研究进行系统评价。结果最终纳入7篇RCT,共529例患者,其中实验组261例（接受Peg-IFNα-2a联合ADV治疗）,对照组268例（接受Peg-IFNα-2a治疗）。系统评价结果显示,相比单药治疗,经联合治疗48 w时CHB患者HBV DNA阴转率显著提高[OR=1.20,95%CI=（1.01,1.43）];48 w时CHB患者HBeAg血清转换率显著提高[OR=1.24,95%CI=（1.02,1.52）],但联合治疗对ALT复常率的影响,系统评价显示结果存在显著偏倚[bias_P=0.012、bias_95 CI=（1.442998,6.467852）],不具有推广性。结论 Peg-IFNα-2a联合ADV治疗HBeAg阳性CHB患者能显著提高患者HBV DNA阴转率及HBeAg血清转换率。

关键词: 慢性乙型肝炎, 聚乙二醇干扰素α, -2a, 阿德福韦酯, 系统评价

Abstract: Objective To investigate the clinical efficacy of pegylated interferon α-2a（Peg-IFNα-2a） combined with adefovir （ADV） in treatment of patients with HBeAg-positive chronic hepatitis B（CHB）. Methods Randomized controlled trials （RCT） involving peg-IFNα-2a combined with adefovir in treatment of patients with HBeAg-positive CHB,were searched from Pubmed,Wanfang Database,Chongqing VIP database,CNKI database,etc,from January,2004 to January,2014,of which the quality were underwent rigorous assessment and data were analyzed by Stata/SE software（version 12）. Results 7 allegeable RCT （a total of 529 cases） were included. There were 261 patients receiving peg-IFNα-2a combined with ADV and 268 receiving peg-IFNα-2a alone. Systematic evaluation showed that HBV DNA negative rate in combinational therapy-treated patients with CHB at the end of week 48 was significantly higher as compared to patients receiving interferon alone[OR=1.20,95% CI=（1.01,1.43）];the HBeAg seroconversion rate at 48 w in patients receiving combinational therapy was also significantly higher than that in the controls[OR=1.24,95% CI=（1.02,1.52）];a significant bias of results was found for serum ALT normalization rate [bias_p=0.012,bias_95 CI=（1.442998,6.467852）]. Conclusions Peg-IFNα-2a combined with ADV significantly improves HBV DNA negative and HBeAg seroconversion rate in patients with HBeAg-positive CHB.

Key words: Chronic hepatitis B, Peg-IFNα-2a, Adefovir, Meta analysis

肖作汉, 孟冈, 王立志. 聚乙二醇干扰素α-2a联合阿德福韦治疗HBeAg阳性慢性乙型肝炎疗效系统评价[J]. 实用肝脏病杂志, 2015, 18(1): 24-29.

Xiao Zuohan, Meng Gang, Wang Lizhi. Clinical efficacy of pegylated interferon α-2a combined with adefovir in treatment of patients with HBeAg-positive chronic hepatitis B:A Meta analysis[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(1): 24-29.

参考文献

[1] Ganem D,Prince AM. Hepatitis B virus infection-natural history and clinicsI conscquence.N Engl J Med,2004,350（2）:1118-1129.
[2] Liaw YF. On-treatment outcome prediction and adjustment during chronic hepatitis B therapy:now and future. Antivir Ther,2009,14（1）:13-22.
[3] Liang X,Bi S,Yang w,et al. Epidemiological serosurvey of hepatitis B in China-declining HBV prevalence due to hepatitis B vaccination. Vaccine,2009,27（3）:6550-6557.
[4] Seeger C,Mason WS.Hepatitis B virus biology.Microbiol MolBiol Rev,2000,64（4）:5l-68.
[5] Liang X,Bi S,Yang W,et aL. Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China. J Infect Dis,2009,200（8）:39-47.
[6] Ahn SH,Kweon YO,Paik SW,et al. Telbivudine in combination with Adefovir versus Adefovir mono therapy in HBeAg-positive,lamivudine-resistant chronic hepatitis B. Hepatol Int,2011,12（10）:448-451.
[7] 樊蓉, 侯金林, 孙剑. 慢性乙型肝炎的个体化治疗策略. 中华内科杂志,2012,51（10）:746-748.
[8] 戎云清. 阿德福韦酯和拉米夫定治疗慢性乙型肝炎疗效对比观察. 实用肝脏病杂志,2012,15（4）:137-138.
[9] Hadziyanllis SJ,Tassopoulos NC,Heathcote EJ,et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med,2005,352（8）:2673-2680.
[10] Wursthorn K,Lutgehetmann M,Dandri M,et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology,2006,44（9）:675-684.
[11] Moher D,Liberati A,Tetzlaff J,et al. Preferred reporting items for systematic reviews and meta-analyses:the PRISMA statement. BMJ,2009,21（7）:339-340.
[12] Leandro G. Meta-analysis in Medical Research. Massachusetts: Blackwell Publishing Ltd,2005,74-78.
[13] European Association for the Study of the Liver.EASL clinical practice guidelines：management of chronic hepatitis B. J Hepatol,2009,50（3）:227-242.
[14] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南（2010年版）. 实用肝脏病杂志,2011,14（2）：81-89.
[15] 科技部十二五重大专项联合课题组专家. 乙型肝炎病毒相关肝硬化的临床诊断、评估和抗病毒治疗的综合管理. 实用肝脏病杂志,2014,17（1）:1-10.
[16] 李静, 李幼平. 不断完善与发展的Cochrane系统评价. 中国循证医学杂志,2008,8（9）:742-743.
[17] Higgins JPT,Green S.Cochrane Handbook for Systematic Reviews of Interventions version 5.0.2.The Cochrane Collaboration,2009,201-203.
[18] TURPIN D L. CONSORT and QUOROM guidelines for reporting randomized clinical trials and systematic reviews. American journal of orthodontics and dentofacial orthopedics:official publication of the American Association of Orthodontists,its constituent societies,and the American Board of Orthodontics,2005,128（6）:681-685.
[19] JAdad AR,Moore RA,Carroll D,et al. Assessing the quality of reports of randomized clinical trials:is blinding necessary. Control Clin Trials,1996,17（1）:1-12.
[20] Walsh C,Walsh S,Tang T,et al. Total abdominal hysterectomy versus total laparoscopic hysterectomy for benign disease:A meta-analysis. Eur J Obstet Gynecol Reprod Biol,2009,144（1）:1-2.
[21] Liberati A,Altman D G,Tetzlaff J,et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions:explanation and elaboration. BMJ,2009,21（6）：339-340.
[22] 王丹, 翟俊霞, 牟振云, 等. Meta分析中的异质性及其处理方法. 中国循证医学杂志,2009,9（10）:1115-1118.
[23] Brian S E,Torsten H. A handbook of statistical analyses using R. CRC Press,2006:163-169.
[24] 麦劲壮,李河,方积乾,等. Meta分析中失安全系数的估计. 循证医学,2006,6（5）:297-300.
[25] Piccolo P,Lenci I,Demelia L,et al. A randomized controlled trial of pegylated interferon-alpha2a plus adefovir dipivoxil for hepatitis B e antigen-negative chronic hepatitis B. Antivir Ther,2009,14（8）:1165-1174.
[26] 敖飞健,马为民,周伯平. 聚乙二醇干扰素α-2a、阿德福韦酯酯单用及联合应用治疗HBeAg阳性慢性乙型肝炎患者的疗效及安全性比较. 中华传染病杂志,2010,28（4）:214-217.
[27] 李月波, 马桂芹, 许蕾,等. PeglFNa-2a联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的临床疗效观察. 中华临床感染病杂志,2008,l（3）:168-170.
[28] 万继红,刘凤霞. 聚乙二醇干扰素a-2a联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎患者疗效观察. 中国保健营养,2012,22（11）:4351-4352.
[29] 杨永锐,李晖,贾婷,等. 聚乙二醇干扰素α-2a联合阿德福韦酯治疗HBeAg阳性慢性乙肝. 昆明医科大学学报,2012,33（10）:106-108.
[30] 李文兵,丁继光,孙庆丰,等. 聚乙二醇干扰素α-2a与阿德福韦酯联合治疗HBeAg阳性慢性乙型肝炎患者的研究. 中华医院感染学杂志,2013,23（6）:1250-1252.
[31] 张雪红,易长庚. 阿德福韦酯联合聚乙二醇干扰素α-2a治疗慢性乙型肝炎的疗效观察. 现代医药卫生,2014,11（11）:1637-1638.
[32] Wursthom K,Lutgehetmann M,Dandri M,et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HbsAg reduction in patients with chronic hepatitis B. Hepatology,2006,44（3）:675-684.
[33] 窦晓光,徐道振,翁心华. 当前聚乙二醇干扰素治疗慢性乙型肝炎的热点与难点. 中华传染病杂志,2010,28（4）:201-203.
[34] Olinger CM,Jutavijittum P,Hubschen JM,et a1. Possible new hepatiffs B virus genotype,southeast Asia. Emerg Infect Dis,2008,14（2）:1777-1780.
[35] 中华医学会肝病学分会肝癌学组. HBV/HCV相关性肝细胞癌抗病毒治疗专家建议. 中华肝脏病杂志,2013,21（2）:96-100.
[36] 王蜀强,徐开菊,吴家箴,等. 不同疗程干扰素联合核苷（酸）类似物治疗HBeAg阳性慢性乙型肝炎的疗效. 中华肝脏病杂志,2011,19（10）:785-787.
[37] Li C,Ji H,Cai Y,et al. Serum interleukin-37 concentrations and HBeAg seroconversion in chronic HBV patients during telbivudine treatment. J Interferon Cytokine Res,2013,22（5）114-117.
[38] Johnson N,Barlow D,Lethaby A,et al. Methods of hysterectomy:systematic review and meta-analysis of randomised controlled trials. BMJ,2005,330（7506）:1478-1480.