慢性HBV感染者血清HBsAg自发转阴的影响因素分析

Analysis of Influence Factors Resulting to HBsAg Spontaneous Seroclearance in Chronic Hepatitis B Infection Patients

【目的】通过对大队列的慢性HBV感染者长期随访观察,了解自然状态下血清HBsAg转阴情况及其影响因素。【方法】选取中山大学附属第三医院974例未抗病毒的慢性HBV感染者为研究对象,定期收集患者临床数据,包括人口学数据、基线及随访各时间点的生化学、病毒学、血清学、肝脾影像学指标,了解其血清HBsAg自发转阴情况,并进行单因素和多因素COX回归分析。【结果】随访至2016年12月,974例慢性HBV感染者中共54例出现血清HBsAg自发转阴,每年自发阴转率约为1.3%。单因素分析发现:年龄(特别是≥50岁,HR值为2.647,P=0.001)、BMI(特别是≥28,即特别肥胖者,HR值为3.401,P=0.004)、基线HBV DNA水平(特别是<104U/m L,HR值为11.798,P=0.001)、基线HBeAg状态(HR值为0.192,P=0.001)、基线HBsAg滴度(特别是>2 000 U/m L,HR值为0.056,P<0.001)、脾长径(HR值为1.017,P=0.013)、右肝斜径(HR值为1.026,P=0.007),是血清HBsAg转阴的影响因素。多因素分析发现,基线HBsAg滴度(HR值为0.071,P<0.001)、基线HBV DNA(HR值为0.819,P=0.005)是血清HBsAg转阴的独立影响因素。【结论】慢性HBV感染者血清HBsAg自发转阴与多种因素相关,其中基线HBV DNA水平、基线HBsAg水平为独立影响因素,基线HBV DNA水平越低(≤104U/m L)、基线HBsAg低水平(≤2 000 U/m L)者更易发生血清HBsAg转阴。

【Objective】To screen the factors that may affect HBsAg spontaneous seroclearance and to explore the real-life situation of HBsAg spontaneous seroclearance in a large cohort of chronic hepatitis B infection patients with longterm follow-up.【Method】All the patients came from the SCHEMA cohort（South China Hepatitis Monitoring and Administration cohort）with chronic HBV infection who were followed up in the out-patient department of the third affiliated hospital,Sun Yat-sen University from Jan. 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 indicators during the follow-up period,and then univariate and multivariate COX regression model were taken to screen the influence factors.【Result】54 patients obtained HBsAg spontaneous seroclearance in 974 chronic hepatitis B infection patients after up to 10 years follow-up. We found that age（especially≥50,HR=2.647,P=0.001）,BMI（especially≥28,which means very fat,HR=3.401,P=0.004）,baseline HBV DNA level（especially〈104 U/m L,HR=11.798,P=0.001）,portal length（HR=1.017,P=0.013）,right liver oblique diameter（HR=1.026,P=0.007）and baseline HBsAg titer（especially2000 U/m L,HR=0.056,〈P0.001）can significantly affect HBsAg seroclearance by univariate COX regression analysis.In the multivariate COX regression analysis,baseline HBsAg titer（HR=0.071,P〈0.001）and baseline HBV DNA quantitation（HR = 0.819,P = 0.005）had an independent effects on HBsAg spontaneous seroclearance.【Conclusion】For the chronic hepatitis B infection patients without antiviral treatment,Baseline HBV DNA levels and baseline HBsAg levels were independent factors of HBsAg spontaneous seroconversion. Moreover,the patients with baseline HBV DNA lower levels（〈104 U/m L）and HBsAg lower levels（〈2 000 U/m L）were more likely to obtain HBsAg spontaneous seroclearance.