尿肝型脂肪酸结合蛋白(L-FABP)对慢加急性肝衰竭短期预后的预测价值  

Value of urinary liver fatty acid-binding protein in predicting the short-term prognosis of patients with acute-onchronic liver failure

作　　者：吴华兰 洪畅泽 蒋秀华 陈金军[1,2,3,4,5] WU Hualan;HONG Changze;JIANG Xiuhua;CHEN Jinjun(Department of Hepatology Unit and Infectious Diseases,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;Hepatology Unit,Zengcheng Branch,Nanfang Hospital,Southern Medical University,Guangzhou 511300,China;State Key Laboratory of Organ Failure Research,Guangzhou 510515,China;Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Guangzhou 510515,China;Key Laboratory of Infectious Diseases Research in South China,Ministry of Education,Guangzhou 510515,China)

机构地区：[1]南方医科大学南方医院感染内科,广州510515 [2]南方医科大学南方医院增城分院肝病中心,广州511300 [3]器官衰竭防治国家重点实验室,广州510515 [4]广东省病毒性肝炎研究重点实验室,广州510515 [5]华南传染病防治教育部重点实验室,广州510515

出　　处：《临床肝胆病杂志》2024年第8期1639-1645,共7页Journal of Clinical Hepatology

基　　金：国家重点研发专项(2022YFC2304800);国家自然科学基金(82370614,82070650);国家科技部重大专项(2018ZX10723203);广东省珠江人才计划(2017BT01S131);南方医院“临床研究专项”(2018CR037,2020CR026);南方医科大学临床启动计划(LC2019ZD006);南方医院院长基金(2019Z003);广东省重点领域研发计划(2019B020227004)。

摘　　要：目的探讨肝型脂肪酸结合蛋白(L-FABP)对慢加急性肝衰竭(ACLF)患者严重程度及短期预后的预测价值。方法研究对象149例来自于一个评估ACLF患者血小板功能的前瞻性、多中心队列,根据入院28天预后分为生存组(n=97)与死亡组(n=52)。分析患者的性别、年龄、病因以及入院后24 h内的血常规、生化指标、器官衰竭情况并检测尿液及血液中LFABP水平。正态分布的计量资料2组间比较使用成组t检验;非正态资料分布的计量资料2组间比较采用Mann-Whitney U检验;计数资料2组间比较采用χ^(2)检验。Spearman相关性检验评估尿L-FABP与肝衰竭相关指标的相关性。绘制受试者工作特征曲线(ROC曲线)评价CLIF-OFs、MELD评分和尿L-FABP对于ACLF患者短期预后的预测价值;通过Kaplan-Meier分析尿L-FABP高水平组与低水平组患者短期死亡情况;采用Cox风险比例模型分析各因素对ACLF短期预后的影响。结果两组患者在白细胞计数、血清TBil、INR、CLIF-OFs、MELD评分和尿L-FABP水平;脑衰竭、肝衰竭、凝血衰竭、肾脏衰竭、呼吸衰竭的比例方面差异均有统计学意义(P值均<0.05)。相关性分析结果显示,尿L-FABP与血清TBil呈显著正相关(r=0.225,P=0.006)。尿L-FABP水平预测28天预后的ROC曲线下面积(AUC)为0.804(95%CI:0.729~0.865,P<0.001),截断值为4.779µg/dL(敏感度为73.08%,特异度为73.91%,约登指数为0.4699)。Kaplan-Meier生存分析发现,相比于尿L-FABP低水平组(尿L-FABP≤4.779µg/dL),尿L-FABP高水平组(尿L-FABP>4.779µg/dL)28天生存率显著降低(P<0.001)。Cox风险比例模型分析发现,血清TBil(HR=1.003,95%CI:1.001~1.004)、CLIF-OFs(HR=2.283,95%CI:1.814~2.873)和高尿L-FABP水平(HR=4.568,95%CI:2.424~8.608)为ACLF短期预后的独立危险因素(P值均<0.05)。结论高尿L-FABP水平可作为ACLF短期预后的临床预测指标,需扩大样本量进一步验证其预测价值。Objective To investigate the value of liver fatty acid-binding protein(L-FABP)in predicting the severity and shortterm prognosis of patients with acute-on-chronic liver failure(ACLF).Methods A total of 149 patients with ACLF were selected from a prospective multicenter cohort assessing the platelet function of ACLF patients,and according to the 28-day prognosis after admission,they were divided into survival group with 97 patients and death group with 52 patients.The patients were analyzed in terms of sex,age,etiology,and blood routine,biochemical parameters,and organ failure status within 24 hours after admission,and the level of L-FABP in urine and blood was measured.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman test was used to evaluate the correlation between urinary L-FABP and indicators for liver failure.The receiver operating characteristic(ROC)curve was plotted to assess the value of CLIF-OFs,MELD score,and urinary L-FABP in predicting the shortterm prognosis of ACLF patients;the Kaplan-Meier analysis was used to evaluate short-term mortality in the high urinary L-FABP group and the low urinary L-FABP group;the Cox proportional hazards model was used to investigate the association of each factor with the short-term prognosis of ACLF.Results There were significant differences between the two groups in white blood cell count,serum total bilirubin(TBil),international normalized ratio,CLIF-OFs,MELD score,urinary L-FABP level,and the proportion of patients with cerebral failure,liver failure,coagulation failure,renal failure,or respiratory failure(all P<0.05).The Spearman correlation analysis showed that urinary L-FABP was significantly positively correlated with serum TBil(r=0.225,P=0.006).Urinary L-FABP level had an area under the ROC

关 键 词：慢加急性肝功能衰竭 肝硬化 脂肪酸结合蛋白质类 预后 

分 类 号：R575.3[医药卫生—消化系统]