非活动性HBsAg携带者HBV再激活及其临床特征  

Incidence and clinical characteristics of HBV reactivation in inactive hepatitis B virus surface antigen carriers

作　　者：廖雪姣[1] 孙丽琴[2] 董京科 张丽娜[1] 马拯华 韦秋煜 郑国琴[1] 刘甲野 Liao Xuejiao;Sun Liqin;Dong Jingke;Zhang Lina;Ma Zhenghua;Wei Qiuyu;Zheng Guoqin;Liu Jiaye;无(Institute of Hepatology,Shenzhen Third People’s Hospital,Shenzhen 518112,Guangdong Province,China;Department of Infectious Diseases,Shenzhen Third People’s Hospital,Shenzhen 518112,Guangdong Province,China;School of Public Health,Shenzhen University,Shenzhen 518060,Guangdong Province,China;Department of Immune Prevention Management,Shandong Provincial Center for Disease Control and Prevention,Jinan 250014,China)

机构地区：[1]深圳市第三人民医院肝病研究所,广东深圳518112 [2]深圳市第三人民医院感染科,广东深圳518112 [3]深圳大学公共卫生学院,广东深圳518073 [4]山东省疾病预防控制中心免疫预防管理所,济南250014

出　　处：《中国肝脏病杂志（电子版）》2021年第4期54-63,共10页Chinese Journal of Liver Diseases：Electronic Version

基　　金：国家自然科学基金(81803299);深圳市基础研究专项(JCYJ20190809160213289);山东省自然科学基金(ZR2019PH046);山东省医药卫生科技发展计划项目(2015WS0285)。

摘　　要：目的探讨非活动性乙型肝炎病毒表面抗原(hepatitis B virus surface antigen,HBs Ag)携带者乙型肝炎病毒(hepatitis B virus,HBV)再激活的发生率及临床特征。方法以2014年1月至2019年12月于深圳市第三人民医院随访的64例非活动性HBsAg携带者为研究对象,6~12个月随访1次,收集HBV再激活发生情况、肝功能[包括丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBil)和γ-谷氨酰转移酶(gammaglutamyltransferase,GGT)]及肝组织病理学结果、HBV再激活发生后的临床结局等。采用Kaplan-Meier法估计累积HBV再激活率;采用单因素和多因素Cox比例风险模型进行HBV再激活的影响因素分析。结果与基线相比,发现HBV再激活时研究对象的ALT[7.69%(2/26)vs 0%(0/26)]、AST[0%(0/26)vs 0%(0/26)]、TBil[19.23%(5/26)vs 19.23%(5/26)]和GGT[3.85%(1/26)vs 0%(0/26)]异常率差异均无统计学意义(P均>0.05)。基线和发现HBV再激活时研究对象HBV DNA≥2000 IU/ml比例分别为0%(0/26)、46.15%(12/26),差异有统计学意义(χ^(2)=15.600,P<0.001);HBV再激活者基线HBeAg均为阴性,发现HBV再激活时有1例HBeAg复阳(P=1.000)。HBV再激活后共6例进行了肝脏穿刺病理检查,4例为G1S1,1例为G1-2S2,1例为G1S2。多因素Cox比例风险模型分析表明基线HBVDNA≥100IU/ml者发生HBV再激活的风险是基线HBV DNA<100 IU/ml者的2.62倍(HR=2.62,95%CI:1.04~6.58,P=0.041)。随访12个月时累积HBV再激活率为37.1%(26/64,95%CI:21.4%~49.6%)。基线HBVDNA≥100IU/ml者随访12个月时累积HBV再激活率(43.8%,95%CI:22.4%~59.3%)显著高于基线HBV DNA<100 IU/ml者(24.3%,95%CI:2.9%~40.9%),差异有统计学意义(Log-rankχ^(2)=4.50,P=0.03)。HBV再激活后的2次随访发现,累积3例未经抗病毒治疗实现病毒学抑制,5例启动抗病毒治疗后实现了病毒学抑制,1例实现HBsAg自发清除;随访患者ALT均在正常范围内。结论非活动性HBs Ag携Objective To investigate the incidence and clinical characteristics of hepatitis B virus(HBV)reactivation in inactive hepatitis B virus surface antigen(HBsAg)carriers.Methods A total of 64 inactive HBsAg carriers in Shenzhen Third People’s Hospital from January 2014 to December 2019 were enrolled and followed up every 6~12 months.Information including HBV reactivation,liver biochemistry[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil)and gamma-glutamyltransferase(GGT)],pathological characteristics of liver injury and outcomes of HBV reactivation were collected during the following-up.Kaplan-Meier method was used to estimate cumulative probabilities of HBV reactivation and multivariable Cox proportional hazards model was used to explore the risk factors of HBV reactivation.Results Compared with baseline,there were no significant differences on the abnormal rate of ALT[7.69%(2/26)vs 0%(0/26)],AST[0%(0/26)vs 0%(0/26)],TBil[19.23%(5/26)vs 19.23%(5/26)]and GGT[3.85%(1/26)vs 0%(0/26)]of objects when HBV reactivation was found.The ratio of objects with HBV DNA≥2000 IU/ml were 0%(0/26)and 46.15%(12/26)on baseline and when HBV reactivation was found,respectively,and the difference was statistically significant(χ^(2)=15.600,P<0.001).HBeAg of objects with HBV reactivation was negative on baseline,and there was one case whose HBeAg converted from negative to positive when HBV reactivation was found(P=1.000).A total of six cases underwent liver puncture pathology after HBV reactivation,among whom four patients presented G1 S1,one presented G1-2 S2 and one presented G1 S2,respectively.Multivariable Cox proportional hazards model showed that patients with baseline HBV DNA≥100 IU/ml had a 2.62-fold risk of HBV reactivation than those with baseline HBV DNA<100 IU/ml(HR=2.62,95%CI:1.04~6.58,P=0.041).The cumulative probabilities of HBV reactivation was 37.1%(26/64,95%CI:21.4%~49.6%)at 12 months of follow-up.The cumulative probabilities of HBV reactivation in patients with baseline HBV DNA�

关 键 词：HBSAG携带者 非活动性 HBV再激活 发生率 影响因素 临床特征 

分 类 号：R512.62[医药卫生—内科学]