合并MAFLD的慢性HBV感染者显著肝纤维化的无创模型建立与验证  

Establishment and validation of a non-invasive model of significant liver fibrosis in chronic HBV infected patients with MAFLD

作　　者：区蓝芯 黄柏盛 张莹洁 施梅姐[2] 张朝臻[2] 萧焕明[2] OU Lanxin;HUANG Baisheng;ZHANG Yingjie;SHI Meijie;ZHANG Chaozhen;XIAO Huanming(The Second Clinical Medical College,Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405;Department of Hepatology,Guangdong Provincial Hospital of Traditional Chinese Medicine,China)

机构地区：[1]广州中医药大学第二临床医学院,广东广州510405 [2]广东省中医院肝病科

出　　处：《胃肠病学和肝病学杂志》2024年第1期15-19,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家“十三五”重大传染病专项课题(2018ZX10725506-003,2018ZX10725505-004);广东省中医院院内专项(YN2022DB04,YN10101903,YN2016XP03);池晓玲国家中医药管理局名老中医药专家传承工作室项目(国中医药人教函[2022]75号);第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号);广东省名中医传承工作室建设项目(粤中医办函[2018]5号);广东省中医药局科研项目(20211189,20225022,20191156)。

摘　　要：目的 探究合并代谢相关性脂肪性肝病(metabolic associated fatty liver disease,MAFLD)的慢性HBV感染患者发生显著肝纤维化的危险因素,构建并验证预测肝组织显著肝纤维化的无创模型,为临床启动抗纤维化治疗提供思路。方法 回顾性收集2015年1月至2020年12月就诊于广东省中医院肝病科收治的合并MAFLD的慢性HBV感染患者445例,根据入院时间分为训练队列(n=274)和验证队列(n=171)。训练队列中根据病理结果分为无/轻微肝纤维化组(<S_(2)期,n=106)和显著肝纤维化组(≥S_(2)期,n=168),比较两组患者临床指标,多因素Logistic回归方法筛选显著肝纤维化的危险因素,ROC曲线评价无创模型的预测效能,并在验证队列中验证。结果 445例患者中,肝组织显著纤维化287例(63.08%),其中训练队列168例(61.31%)、验证队列119例(69.59%)。训练队列中,≥S_(2)期组患者的年龄、ALT、AST、ALP、GGT、PT、HBsAg、HBV DNA、LSM均高于<S_(2)组,WBC、RBC、PLT、TG、Urea均低于<S_(2)组(P<0.05)。多因素分析显示,年龄、GGT、HBV DNA、LSM均是显著肝纤维化的独立危险因素(P<0.05),Urea是保护因素(P<0.05)。根据年龄、GGT、Urea、HBV DNA和LSM建立无创模型Y=0.063×年龄(岁)+0.016×GGT(U/L)+0.246×HBV DNA(lg IU/L)+0.245×LSM(kPa)-0.484×Urea(mmol/L)-3.578,在训练队列中预测肝组织显著纤维化预测效能均高于APRI、FIB-4(P<0.05),取敏感度与特异度最大时的点的临界值Y=0.70,此时预测敏感度为62.5%,特异度为92.5%;在验证队列中,预测效能均高于APRI、FIB-4(P<0.05)。结论 年龄、GGT、Urea、HBV DNA和LSM是合并MAFLD的慢性HBV感染患者发生显著肝纤维化的危险因素,由这些参数建立的无创模型对预测该人群发生显著肝纤维化有一定准确性。Objective To explore the risk factors of significant liver fibrosis in chronic HBV infected patients with metabolic associated fatty liver disease(MAFLD),construct and validate a non-invasive model to predict significant liver fibrosis in liver tissue,and provide ideas for clinical initiation of anti fibrosis therapy.Methods A total of 445 chronic HBV infection with MAFLD who were admitted to the Department of Hepatology,Guangdong Provincial Hospital of Traditional Chinese Medicine from Jan.2015 to Dec.2020 were retrospectively collected.They were divided into training cohort(n=274) and validation cohort(n=171) according to the time of admission.The training cohort was divided into no/slight liver fibrosis group(<S_(2) stage,n=106) and obvious fibrosis group(≥S_(2) stage,n=168) according to the pathological results.The clinical indicators of patients in the two groups were compared,and the risk factors of obvious liver fibrosis were screened according to the multifactor Logistic regression method.The prediction efficiency of the non-invasive model was evaluated by ROC curve.And it was verified in the validation cohort.Results Among 445 patients,287 patients(63.08%) had significant liver fibrosis,including 168 patients(61.31%) in the training cohort and 119 patients(69.59%) in the validation cohort.In the training cohort,the age,ALT,AST,ALP,GGT,PT,HBsAg,HBV DNA,LSM of patients in ≥S_(2) group were higher than those in <S_(2) group,while WBC,RBC,PLT,TG,Urea were lower than those in <S_(2) group(P<0.05).Multivariate analysis showed that age,GGT,HBV DNA,LSM were independent risk factors for significant liver fibrosis(P<0.05),and Urea was a protective factor(P<0.05).Establish non-invasive model according to age,GGT,Urea,HBV DNA and LSM:Y=0.063×age(year)+0.016×GGT(U/L)+0.246×HBV DNA(lg IU/L)+0.245×LSM(kPa)-0.484×Urea(mmol/L)-3.578,in the training cohort,the AUC for predicting significant liver fibrosis was 0.827,which was higher than the predictive efficacy of APRI and FIB-4(P<0.05).The critical value Y=0.70 o

关 键 词：代谢相关性脂肪性肝病 慢性HBV感染 显著肝纤维化 危险因素 无创模型 

分 类 号：R575[医药卫生—消化系统]