慢性HBV感染者病毒DNA水平与患者肝组织炎症损伤程度的相关性研究  

Association between HBV viral load and severity of liver inflammation in patients with chronic hepatitis B virus infection

作　　者：邢同京 赵坤宇 李文涛 王雷婕 鲁凤民 Xing Tongjing;Zhao Kunyu;Li Wentao;Wang Leijie;Lu Fengmin(Department of Infectious Diseases,Taizhou Hospital of Zhejiang Province,Linhai 317000,China;Hepatology Institute,Peking University People’s Hospital,Beijing 100044,China;Department of Infectious Diseases,the First Hospital of Jiaxing,Jiaxing 314001,China;Department of Microbiology and Infectious Disease Center,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China)

机构地区：[1]浙江省台州医院感染病科,临海317000 [2]北京大学人民医院北京大学肝病研究所,北京100044 [3]嘉兴市第一医院感染病科,嘉兴314001 [4]北京大学基础医学院病原生物学系暨感染病研究中心,北京100191

出　　处：《中华肝脏病杂志》2023年第9期954-960,共7页Chinese Journal of Hepatology

基　　金：国家自然科学基金(82072280);北京自然科学基金面上项目(7212063)。

摘　　要：目的探讨慢性乙型肝炎病毒(HBV)感染者疾病自然进程中病毒学标志物与宿主抗HBV免疫所致肝脏病理损伤的关系及动态变化。方法回顾性选取2016年1月到2022年6月于浙江省台州医院接受肝穿刺活检的238例成人慢性HBV感染者。收集患者的年龄、性别、血小板、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白蛋白、HBV DNA、qHBsAg、HBeAg等一般临床资料,以及患者的肝组织炎症活动度和纤维化分级等肝脏病理诊断指标。按HBeAg状态对患者进行分组,并分别按不同肝脏炎症活动度、不同HBV DNA载量对患者行亚组分组,统计学分析比较各组的HBV病毒学标志物水平的组间差异,及其与患者肝脏炎症损伤指标如ALT、AST及肝组织炎症活动度间的相关性。结果HBeAg阳性患者中有中度及以上肝脏炎症活动度(G≥2)患者的病毒学标志物水平均显著低于轻(无)炎症活动度(G<2)者(HBV DNA:t=3.102,P=0.002;qHBsAg:Z=-4.859,P<0.001;HBeAg:Z=-4.386,P<0.001);而在HBeAg阴性患者中则呈现相反的趋势,G≥2亚组的HBV DNA水平、qHBsAg显著高于G<2亚组(HBV DNA:t=-5.269,P<0.001;qHBsAg:Z=-2.951,P=0.003)。对应地,HBV DNA水平、qHBsAg在HBeAg阳性患者中与肝脏炎症活动度及肝脏炎症损伤指标AST呈弱到中等强度的负相关(HBV DNA与炎症活动度:r=-0.300,P=0.001;qHBsAg与炎症活动度:r=-0.432,P<0.001;qHBsAg与AST:r=-0.233,P=0.008);而在HBeAg阴性患者中则与肝脏炎症活动度及ALT、AST呈弱到中等强度的正相关(HBV DNA与炎症活动度:r=0.439,P<0.001;HBV DNA与ALT:r=0.502,P<0.001;HBV DNA与AST:r=0.582,P<0.001),其中qHBsAg仅与患者的肝脏炎症活动度呈弱的正相关(r=0.285,P=0.003)。进一步对HBeAg阳性患者按HBV DNA是否>2×106 IU/ml进行亚组分析发现,HBV DNA>2×106 IU/ml亚组的患者其HBV病毒学标志物与肝脏炎症活动度及ALT、AST间呈弱到中等强度的负相关(HBV DNA与炎症活动度:r=-0.276,P=0.009;HBV DNA与AST:r=-0.262,P=0.014;qHBObjective To explore the relationship and dynamic changes between virological markers and hepatic pathological damage due to host anti-hepatitis B virus(HBV)immunity in the natural course of disease in chronic HBV infected patients.Methods Two hundred and thirty-eight adult chronic HBV-infected patients who underwent liver biopsy from January 2016 to June 2022 in Taizhou Hospital,Zhejiang Province,were retrospectively selected.General clinical data such as age,gender,platelets,ALT,AST,albumin,HBV DNA,qHBsAg,HBeAg,and liver pathology diagnostic indexes such as the grade of liver necroinflammation and liver fibrotic stages of the patients were collected.The patients were grouped according to HBeAg status,and subgrouped according to different grades of liver necroinflammation and different HBV DNA loads.Statistical analyses were performed to compare the differences in HBV virologic marker levels between the groups,and the correlation between them and the indicators of hepatic inflammatory injury,such as ALT,AST,and the grade of liver necroinflammation in the patients.Results The levels of HBV virological markers in HBeAg-positive patients with moderate or higher liver necroinflammatory grade(G≥2)were significantly lower than those with mild(no)liver necroinflammatory grade(G<2)(P<0.01);whereas the opposite trend was observed in HBeAg-negative patients,with the levels of HBV DNA,and qHBsAg in the G≥2 subgroup being significantly higher than those in the G<2 subgroup(P<0.01).Correspondingly,HBV DNA level and qHBsAg showed weak to moderately strong negative correlation with liver necroinflammatory grade and AST which was an indicator of hepatic inflammatory injury in HBeAg-positive patients(P<0.05);whereas in HBeAg-negative patients,they showed weak to moderately strong positive correlation with hepatic inflammatory activity and ALT,AST(P<0.001),in which qHBsAg showed only a weak positive correlation with patients'liver necroinflammatory grade(P=0.003).Further subgroup analyses of HBeAg-positive patients according

关 键 词：慢性乙型肝炎 自然疾病进程 乙型肝炎E抗原 乙型肝炎病毒脱氧核糖核酸 乙型肝炎表面抗原定量 免疫病理损伤 

分 类 号：R512.62[医药卫生—内科学]