基于血清学指标的联合模型诊断代偿期肝硬化轻微型肝性脑病的价值  

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis

作　　者：刘尚豪 祖红梅 黄燕[3] 郭小青[4] 向慧玲[5] 党彤[6] 李晓燕 严兆兰 李雅静 刘菲[3] 孙佳 宋瑞欣 闫俊卿[5] 叶青[5] 王晶[6] 孟宪梅[6] 王海英 江振宇[6] 黄磊 孟繁平 张国[9] 王文娟 杨少奇[10] 呼圣娟[11] 阮继刚 雷创[13] 汪清海[13] 田宏玲 郑琦[14] 李异玲[15] 王宁宁[15] 崔会鹏 王滟萌 瞿章书 袁敏 刘益军[17] 陈颖 夏玉香 刘娅媛[18] 刘莹[18] 曲素萱 陶弘 石瑞春 杨小婷 金丹 苏丹 杨永峰[20] 叶伟[21] 刘娜[21] 唐荣瑜 张权 刘琴 邹高亮 李子月[24] 赵彩彦[24] 赵倩[25] 张清格[26] 高华方 孟涛 李婕 吴卫华[27] 王健[27] 杨传龙 吕卉 刘川 王福生 福军亮 祁小龙 Shanghao Liu;Hongmei Zu;Yan Huang;Xiaoqing Guo;Huiling Xiang;Tong Dang;Xiaoyan Li;Zhaolan Yan;Yajing Li;Fei Liu;Jia Sun;Ruixin Song;Junqing Yan;Qing Ye;Jing Wang;Xianmei Meng;Haiying Wang;Zhenyu Jiang;Lei Huang;Fanping Meng;Guo Zhang;Wenjuan Wang;Shaoqi Yang;Shengjuan Hu;Jigang Ruan;Chuang Lei;Qinghai Wang;Hongling Tian;Qi Zheng;Yiling Li;Ningning Wang;Huipeng Cui;Yanmeng Wang;Zhangshu Qu;Min Yuan;Yijun Liu;Ying Chen;Yuxiang Xia;Yayuan Liu;Ying Liu;Suxuan Qu;Hong Tao;Ruichun Shi;Xiaoting Yang;Dan Jin;Dan Su;Yongfeng Yang;Wei Ye;Na Liu;Rongyu Tang;Quan Zhang;Qin Liu;Gaoliang Zou;Ziyue Li;Caiyan Zhao;Qian Zhao;Qingge Zhang;Huafang Gao;Tao Meng;Jie Li;Weihua Wu;Jian Wang;Chuanlong Yang;Hui Lyu;Chuan Liu;Fusheng Wang;Junliang Fu;Xiaolong Qi(The First School of Clinical Medicine,Lanzhou University,Lanzhou 730030,China;Department of Gastroenterology,the Fourth People′s Hospital of Qinghai Provincial,Xining 810099,China;Department of Infectious Diseases,Hunan Key Laboratory of Viral Hepatitis,Xiangya Hospital of Central South University,Changsha 410008,China;Department of Hepatology,the Third People′s Hospital of Taiyuan,Taiyuan 030012,China;Department of Gastroenterology and Hepatology,Tianjin Third Central Hospital,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases,Artificial Cell Engineering Technology Research Center,Institute of Hepatobiliary Disease,Tianjin 300170,China;Department of Gastroenterology,the Second Affiliated Hospital of Baotou Medical College,Baotou 014030,China;Chinese PLA Medical School,Senior Department of Infectious Diseases of the Fifth Medical Center of Chinese PLA General Hospital,National Clinical Research Center for Infectious Diseases,Beijing 100039,China;The Third Central Clinical College of Tianjin Medical University,Tianjin 300270,China;Department of Gastroenterology,the People′s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,China;Department of Gastroenterology,General Hospital of Ningxia Medical University,YinChuan 750003,China;Department of

机构地区：[1]兰州大学第一临床医学院,兰州730030 [2]青海省第四人民医院消化内科,西宁810099 [3]中南大学湘雅医院感染病科病毒性肝炎湖南省重点实验室,长沙410008 [4]太原市第三人民医院肝病科,太原030012 [5]天津市第三中心医院消化肝病科天津市重症疾病体外生命支持重点实验室天津市人工细胞工程技术研究中心天津市肝胆疾病研究所,天津300170 [6]包头医学院第二附属医院消化内科,包头014030 [7]解放军医学院解放军总医院第五医学中心感染病医学部国家感染性疾病临床医学研究中心,北京100039 [8]天津医科大学第三中心临床学院,天津300270 [9]广西壮族自治区人民医院消化内科,南宁530021 [10]宁夏医科大学总医院消化内科,银川750003 [11]宁夏回族自治区人民医院消化内科,银川750002 [12]宁夏医科大学总医院心脑血管病医院消化内科,银川750002 [13]常德市第一人民医院感染科,常德415003 [14]福建医科大学第一附属医院肝内科肝病研究所,福州350004 [15]中国医科大学附属第一医院消化内科,沈阳110001 [16]湘西自治州人民医院感染科,吉首416007 [17]湖南中医药高等专科学校第一附属医院肝病科,株洲412008 [18]丹东市中心医院消化内科,丹东118002 [19]吴忠市人民医院消化内科,吴忠751199 [20]南京市第二医院肝病科,南京210037 [21]南京市第二医院肝硬化治疗中心科,南京210037 [22]南京中医药大学附属南京医院(南京市第二医院),南京210037 [23]贵州医科大学附属医院感染科,贵阳550004 [24]河北医科大学第三医院感染科,石家庄050051 [25]河北医科大学第三医院质量管理与控制办公室,石家庄050051 [26]邢台市人民医院中西医结合肝病科,邢台054001 [27]南京大学医学院附属鼓楼医院感染性疾病科,南京210008 [28]山东省公共卫生临床中心重症肝病科,济南250102 [29]东南大学附属中大医院放射科门静脉高压中心,南�

出　　处：《中华检验医学杂志》2023年第1期52-61,共10页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金(81721002);首都临床诊疗技术研究及转化应用项目(Z201100005520046);天津科技重大专项与工程重大疾病防治(19ZXDBSY00030);包头医学院科学研究基金(BYJJ-QWB202217)。

摘　　要：目的探讨血清学指标对代偿期肝硬化轻微型肝性脑病(MHE)的诊断价值,构建基于血清学指标的联合模型并评估其对MHE的诊断价值。方法前瞻性、多中心研究。选取2021年10月至2022年8月来自我国15个省(自治区、直辖市)的23家医院就诊的代偿期肝硬化患者263例。收集患者临床资料及实验室检查结果,并计算终末期肝病模型(MELD)评分。使用基线血氨测量值/正常参考值上限(AMM-ULN)集中校正各中心血氨测量结果,以我国《肝硬化肝性脑病诊疗指南》标准,数字连接试验-A、数字符号试验均异常作为诊断MHE的标准。基于R语言caret包将患者随机(7∶3)分为训练集(n=185)和验证集(n=78)。通过Logistic回归构建诊断MHE的联合模型;受试者工作特征曲线下面积(AUC)、Hosmer-Lemeshow拟合优度检验及校准曲线图评估诊断性能,并用Bootstrap法(n=200)进行内部验证;Delong检验比较AUC之间的差异。结果训练集中,MHE占37.8%(70/185),MHE组AMM-ULN、白蛋白、血小板、碱性磷酸酶、国际标准化比值、终末期肝病模型评分以及教育年限与无MHE组比较,差异有统计学意义(P均<0.05)。多因素Logistic回归分析显示,AMM-ULN(OR=1.78,95%CI 1.05~3.14,P=0.038)和MELD评分(OR=1.11,95%CI 1.04~1.20,P=0.002)是MHE的独立危险因素,AUC分别为0.663和0.625。联合AMM-ULN、MELD评分和教育年限的联合模型诊断MHE的AUC为0.755,特异度和敏感度分别为85.2%和55.7%。Hosmer-Lemeshow拟合优度检验表明模型具有较好的校准度(P=0.733),联合模型内部验证AUC为0.752。Delong检验显示联合模型诊断效能优于单独使用血氨(P=0.020)和MELD评分(P=0.003)。验证集中,联合模型诊断MHE的AUC为0.794,Hosmer-Lemeshow拟合优度检验显示有较好的校准度(P=0.841)。结论基于AMM-ULN、MELD评分和教育年限的联合模型可提高对MHE的诊断价值。Objective To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy(MHE)in patients with compensated cirrhosis.Methods This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces,autonomous regions and municipalities of China between October 2021 and August 2022.Clinical data and laboratory test results were collected,and the model for end-stage liver disease(MELD)score was calculated.Ammonia level was corrected to the upper limit of normal(AMM-ULN)by the baseline blood ammonia measurements/upper limit of the normal reference value.MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis.The patients were randomly divided(7∶3)into training set(n=185)and validation set(n=78)based on caret package of R language.Logistic regression was used to establish a combined model of MHE diagnosis.The diagnostic performance was evaluated by the area under the curve(AUC)of receiver operating characteristic curve,Hosmer-Lemeshow test and calibration curve.The internal verification was carried out by the Bootstrap method(n=200).AUC comparisons were achieved using the Delong test.Results In the training set,prevalence of MHE was 37.8%(70/185).There were statistically significant differences in AMM-ULN,albumin,platelet,alkaline phosphatase,international normalized ratio,MELD score and education between non-MHE group and MHE group(all P<0.05).Multivariate Logistic regression analysis showed that AMM-ULN[odds ratio(OR)=1.78,95%confidence interval(CI)1.05-3.14,P=0.038]and MELD score(OR=1.11,95%CI 1.04-1.20,P=0.002)were independent risk factors for MHE,and the AUC for predicting MHE were 0.663,0.625,respectively.Compared with the use of blood AMM-ULN and MELD score alone,the AUC of the combined model of AMM-ULN,MELD score and

关 键 词：肝性脑病 肝硬化 血氨 终末期肝病模型评分 诊断模型 

分 类 号：R575.2[医药卫生—消化系统] R575.3[医药卫生—内科学]