慢性HBV感染者核苷(酸)类似物长期治疗HBsAg转阴的影响因素  

Influence Factors Resulting to HBsAg Seroclearance in Chronic Hepatitis B Patients with Long-Term Nucleos(t)ide Analogues Therapy

作　　者：李向永[1] 陈健宁[2] 顾玉荣[1] 尤旭 LI Xiang-yong;CHEN Jian-ning;GU Yu-rong;YOU Xu(Infectious Department,The Third Affiliated Hospital,Sun Yat-sen University,Guangzhou 510630,China;Department of Pathology,The Third Affiliated Hospital,Sun Yat-sen University,Guangzhou 510630,China;The Laboratory Department,The Third Affiliated Hospital,Southern Medical University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院感染科,广东广州510630 [2]中山大学附属第三医院病理科,广东广州510630 [3]南方医科大学第三附属医院检验科,广东广州510630

出　　处：《中山大学学报（医学版）》2018年第6期928-934,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：十二五"重大科技专项(2012ZX10004-902);广东省医学科学技术研究基金(2018366);天河区科技计划项目(201504KW032)

摘　　要：【目的】通过对核苷(酸)类似物(NA)治疗的慢性乙型肝炎(CHB)患者长期随访观察,了解CHB患者的血清HBsAg转阴情况及其影响因素。【方法】回顾性分析1 205例中山大学附属第三医院长期接受核苷(酸)类似物抗病毒的CHB患者的临床资料,包括一般人口学、基线生化学、病毒学、血清学、影像学指标及动态变化,了解其血清HBsAg转阴情况,并进行单因素和多因素COX回归分析。【结果】对1 205例CHB患者随访10年,共50例发生血清HBsAg转阴,每年转阴率为1.0%。单因素分析发现:年龄≥50岁(OR值为1.774,P=0.047)、基线PLT计数(OR值为0.994,P=0.037)、基线HBeAg阴性(OR值为0.335,P=0.001)、脾长径(OR值为1.017,P=0.013)、基线HBsAg滴度(特别是<2000 U/mL,OR值为0.099,P<0.001)、更改抗病毒治疗方案次数(OR值为0.028,P <0.001)、对NA治疗发生病毒学应答(特别是发生IVR、EVR和MR者,OR值为0.028,P <0.001)、发生HBeAg/HBeAb血清学转换者(OR值为12.255,P=0.001),是发生血清HBsAg阴转的影响因素。多因素分析发现:基线HBsAg滴度(OR值为0.172,P <0.001)、更改抗病毒方案次数(OR值为0.095,P <0.001)、是否发生IVR、EVR、MR(OR值为0.018,P <0.001;OR值0.010,P <0.001;OR值0.005,P <0.001)是发生血清HBsAg阴转的独立影响因素。【结论】核苷(酸)类似物治疗的CHB患者血清HBsAg阴转与多种因素相关,基线HBsAg低水平(<2 000 U/mL)、更改抗病毒治疗方案的次数越少、病毒应答的越早、越快,病毒应答后持续时间越久者,更易发生血清HBsAg转阴。【Objective】To screen the factors that may affect HBsAg seroclearance and to explore the real-life situa?tion of HBsAg seroclearance in a large cohort of chronic hepatitis B patients with long-term Nucleos(t)ide analogues(NA)therapy.【Method】All the patients came from the SCHEMA cohort(South China Hepatitis Monitoring and Admin?istration cohort)with chronic HBV infection who were followed up in the out-patient department of the third affiliated hospital,Sun Yat-sen University from January 2006.The data were regularly collected at 3 or 6 months interval,including demographic characteristics,baseline,dynamic changes of the biochemical,virological,serological and imagery indica?tors during the follow-up period,and then univariate and multivariate COX regression model were taken to screen the in?fluence factors.【Result】50 patients obtained HBsAg seroclearance in 1205 chronic hepatitis B patients with long-term NA therapy after up to 10 years follow-up,and the HBsAb seroclearance rate was 1.0%.We found that age(especially≥50,HR=1.774,P=0.0476),baseline PLT mount(HR=0.994,P=0.037),baseline HBeAg status(HR=0.335,P=0.001),spleen length(HR=1.017,P=0.013),baseline HBsAg titer(especially<2000 IU/mL,HR=0.099,P<0.001),the numbers of changed antiviral therapy(HR=0.028,P<0.001),obtained virological response to NA(espe?cially obtained IVR,EVR,MR,HR=0.028,P<0.001)and obtained HBeAg/HBeAb seroclearance(HR=12.225,P=0.001)can significantly affect HBsAg seroclearance by univariate COX regression analysis.In the multivariate COX regression analysis,baseline HBsAg level(HR=0.172,P<0.001),the numbers of changed antiviral therapy(HR=0.095,P<0.001),obtained IVR(HR=0.018,P<0.001),EVR(HR=0.010,P<0.001),MR(HR=0.005,P<0.001)had an independent effects on HBsAg seroclearance.【Conclusion】For the chronic hepatitis B patients with longterm NA therapy,baseline HBsAg level,the numbers of changed antiviral therapy and obtained IVR,EVR,MR were in?dependent factors of HBsAg seroconversion.Moreover,the patients with baseline HBsAg lower

关 键 词：核苷(酸)类似物 慢性乙型肝炎 HBSAG 影响因素 

分 类 号：R51[医药卫生—内科学]