细胞因子水平在重症乙型肝炎患者表面抗原清除中的临床意义初探  

Clinical significance of cytokine levels in HBsAg sero-clearance in patients with severe hepatitis B

作　　者：向小梅 万星 张娟 肖剑梅 王昊亮 谷冬晴 邓国宏 XIANG Xiaomei;WAN Xing;ZHANG Juan;XIAO Jianmei;WANG Haoliang;GU Dongqing;DENG Guohong(Department of Infectious Diseases,Chongqing Key Laboratory of Precision Diagnosis and Treatment for Uiral Infectious Diseases,First Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400038,China)

机构地区：[1]陆军军医大学(第三军医大学)第一附属医院感染病科,病毒传染病精准防治重庆市重点实验室,重庆400038

出　　处：《陆军军医大学学报》2024年第16期1913-1919,共7页Journal of Army Medical University

基　　金：国家自然科学基金重点项目(81930061)。

摘　　要：目的探讨细胞因子的表达在重症乙型肝炎患者表面抗原(hepatitis B surface antigen,HBsAg)清除中是否具有临床意义。方法采用巢氏病例-对照研究设计,纳入2006-2020年陆军军医大学第一附属医院感染病科住院的14例重症乙型肝炎患者作为研究对象,其中7例在肝炎活化1年内HBsAg发生清除(HBsAg清除组),年龄(36.57±3.15)岁;7例在1年内HBsAg下降少于1个lg(HBsAg未清除组),年龄(34.14±2.97)岁。采用Luminex液相芯片技术检测14例重症乙型肝炎患者入院时血清样本中IFN-γ、IL-2等48种细胞因子表达水平。结果HBsAg清除组中3种细胞因子(IFN-γ、IL-2Ra、SDF-1α)表达水平显著低于HBsAg未清除组(P<0.05),其余39种细胞因子表达水平在2组间差异无统计学意义,另5种未在2组间同时表达。血清HBV DNA水平与HGF(r=0.675,P=0.008)及SDF-1α(r=0.587,P=0.027)表达水平呈正相关;与IP-10(r=-0.600,P=0.023)及MIG(r=-0.640,P=0.014)表达水平呈负相关。HBsAg滴度与IL-12p70表达水平呈正相关(r=0.593,P=0.025),与TNF-α表达水平呈负相关(r=-0.609,P=0.021)。血清总胆红素水平与SCGF-β表达水平呈正相关(r=0.543,P=0.045)。结论本研究找到3种差异表达细胞因子及一些与HBV DNA水平、HBsAg滴度相关的细胞因子,可为肝炎活化引起HBV病毒清除的免疫学机制研究提供新思路。同时,为重症乙型肝炎患者HBsAg血清学清除提供潜在标志物。Objective To explore the clinical significance of serum cytokine expression in the hepatitis B surface antigen(HBsAg)sero-clearance in patients with severe hepatitis B.Methods A nested case-control trial was conducted on 14 inpatients with severe hepatitis B admitted in our hospital from 2006 to 2020.Of them,7 patients(aged 36.57±3.15 years)achieved HBsAg sero-clearance within 1 year after the onset of hepatitis B flares(with abrupt rise of ALT level to>5 times the upper limit of normal during HBV infection)and were assigned into HBsAg clearance group,while the other 7 patients(aged 34.14±2.97 years)only obtained HBsAg decreased less than 1 g within 1 year after the onset(HBsAg non-clearance group).Then,multiplex liquid-chip assay based on Luminex xMAP was used to detect the expression levels of 48 cytokines such as IFN-γand IL-2 in serum samples of these 14 patients.Results The serum levels IFN-γ,IL-2Ra and SDF-1αwere significantly lower in the HBsAg clearance group than the HBsAg non-clearance group(P<0.05),but no statistical differences were observed in other 39 cytokines between the 2 groups.And there were 5 cytokines having no mutual expression in both groups.The copy number of HBV DNA was positively correlated with serum HGF(r=0.675,P=0.008)and SDF-1αlevels(r=0.587,P=0.027),while negatively with IP-10(r=-0.600,P=0.023)and MIG level(r=-0.640,P=0.014).Meanwhile,a positive correlation was found between HBsAg titer and IL12-p70 level(r=0.593,P=0.025),and a negative correlation between HBsAg titer and TNF-αlevel(r=-0.609,P=0.021).In addition,the serum total bilirubin level was positively correlated with the expression of SCGF-β(r=0.543,P=0.045).Conclusion Three differentially expressed cytokines and some cytokines related to HBV DNA level and HBsAg titer are found,which may provide new insights into the underlying immunological mechanism of HBV virus clearance caused by hepatitis flares.Meanwhile,it also provides potential biomarkers for HBsAg serological clearance in patients with severe hepatitis B.

关 键 词：重症乙型肝炎 HBsAg清除 临床治愈 细胞因子 

分 类 号：R392.11[医药卫生—免疫学] R446.112[医药卫生—基础医学] R512.62