摘要目的 系统评价慢性乙型肝炎(CHB)患者停用核苷(酸)类药物后复发的相关因素.方法 检索在PubMed、万方数据、维普期刊、中国知网全文数据库、读秀学术搜索和中国生物医学文献数据库发表的有关CHB患者停药后复发的相关文献.应用RevMan 5.3软件进行荟萃分析.根据异质性差异采用随机效应或固定效应模型,以加权均数差(WMD)或比值比(OR)分别表示连续变量和二分类变量的效应量.采用Stata SE 11.0软件进行发表偏倚分析.结果 共筛选出20篇文献纳入研究,均为病例对照研究,HBeAg阳性患者核苷(酸)类药物停药3个月、6个月、1年的复发合并率分别为21.0％、30.4％和33.2％.HBeAg阴性患者停药3个月、6个月、1年的复发合并率分别为26.5％、34.1％和50.1％.单独分析停用拉米夫定患者,发现3个月、6个月、1年的复发合并率分别为21.0％、28.0％和34.3％.荟萃分析结果显示:在使用核苷(酸)类药物HBeAg阳性的CHB患者中,复发组年龄(WMD=7.36,95％ CI:5.72～9.00,Z=8.81,P＜0.01)、基线HBV DNA水平(WMD=0.26,95％ CI:0.05 ～0.46,Z=2.44,P=0.01)大于未复发组,抗病毒疗程短于未复发组(WMD=-3.12,95％ CI:-4.56～-1.68,Z=4.26,P＜0.01),合并肝硬化患者复发率高于无肝硬化患者(OR=2.59,95％ CI:1.33 ～5.04,Z=2.79,P＜0.01).在使用核苷(酸)类药物的HBeAg阴性患者中,复发组年龄大于未复发组(WMD=5.90,95％ CI:1.57～10.23,Z=2.67,P＜0.01),其他相关因素比较差异无统计学意义(P＞0.05).单独使用拉米夫定的CHB患者,复发组年龄(WMD=7.68,95％ CI:5.02 ～ 10.34,Z=5.66,P＜0.01)、基线HBV DNA水平(WMD=0.26,95％ CI:0.05～0.46,Z=2.44,P=0.01)大于未复发组,抗病毒疗程小于未复发组(WMD=-2.11,95％ CI:-3.85 ～-0.38,Z=2.39,P＜0.05),合并肝硬化患者复发率高于无肝硬化患者(OR=2.59,95％ CI:1.33 ～5.04,Z=2.79,P＜0.01).结论 在使用核苷(酸)类药物的HBeAg阳性和单独使用拉米夫定的CHB患者中,年龄、基线HBV DNA水平、抗病毒疗程、肝硬化均是影响核苷(酸)类药物停药后复发的相关因素,而在HBeAg阴性患者中,仅年龄是影响复发的相关因素.

abstractsObjective To evaluate the factors associated with recurrence of chronic hepatitis B (CHB) after nucleoside analogs (NAs) withdrawal.Methods A literature search from PubMed,Wanfang data,CQVIP,CNKI,Duxiu and SinoMed was conducted to identify studies on the recurrence of CHB after NAs withdrawal.Meta-analysis was performed using RevMan 5.3.Random-effects or fixed-effects model was performed based on the heterogeneity.Weighted mean difference (WMD) was used to assess the continuous data,and odds ratio (OR) was used to assess the dichotomous data.Publication bias was evaluated with Egger' s regression test using Stata SE 11.0.Results A total of 20 case-control studies were included in this analysis.The recurrence rates were 21.0％,30.4％,33.2％ in HBeAg-positive CHB patients,and 26.5％,34.1％,50.1％ in HBeAg-negative patients after NAs withdrawal for 3 months,6 months and 1 year,respectively.For patients treated with lamivudine,the recurrence rates of CHB were 21.0％,28.0％,34.3％ at 3-,6-and 12-month after NAs withdrawal.Meta analysis demonstrated that among HBeAg-positive CHB patients,the average age (WMD =7.36,95％ CI:5.72-9.00,Z =8.81,P ＜0.01) and baseline HBV DNA level (WMD =0.26,95％ CI:0.05-0.46,Z =2.44,P =0.01) were higher in recurrence group,while antiviral treatment duration was shorter in recurrence group (WMD =-3.12,95％ CI:-4.56--1.68,Z =4.26,P ＜ 0.01),and the rate of recurrence was higher in patients with liver cirrhosis (OR =2.59,95％ CI:1.33-5.04,Z =2.79,P ＜ 0.01).Among HBeAg negative patients,the average age of patients in recurrence group was higher than that in non-recurrence group (WMD =5.90,95％ CI:1.57-10.23,Z =2.67,P ＜ 0.01),and no difference was observed in other factors between recurrence and non-recurrence patients.Among patients treated with lamivudine,the average age (WMD =7.68,95％ CI:5.02-10.34,Z =5.66,P ＜0.01) and baseline HBV DNA level (WMD =0.26,95％ CI:0.05-0.46,Z =2.44,P =0.01) were higher,while antiviral treatment duration was shorter in recurrence group (WMD=-2.11,95％CI:-3.85--0.38,Z=2.39,P＜0.01),and the rate of recurrence was higher in patients with liver cirrhosis (OR =2.59,95％ CI:1.33-5.04,Z =2.79,P ＜ 0.05).Conclusion Among HBeAg-positive and lamivudine-treated patients,age,baseline HBV DNA level,antiviral treatment duration and liver cirrhosis are associated with the recurrence of CHB after NAs withdrawal; while for HBeAg-negative patients,age is the only risk factor.