血清MMP-7检测在梗阻性黄疸鉴别诊断中的价值:多中心临床诊断准确性研究  

Value of serum matrix metalloproteinase-7 in the differential diagnosis of obstructive jaundice:a multicenter diagnostic trial

作　　者：姜璟㼆 方焯 董瑞[1] 邓嘉乐 谢新宝[3] 杨大可 陈功[1] 孙松[1] 项唯唯 吴颖[1] 张中喜 任红霞[5] 钭金法[6] 唐维兵[7] 吕尚耀 李文[9] 黄玉梅[10] 祁正红 郑珊[1] Jiang Jingying;Fang Zhuo;Dong Rui;Deng Jiale;Xie Xinbao;Yang Dake;Chen Gong;Sun Song;Xiang Weiwei;Wu Ying;Zhang Zhongxi;Ren Hongxia;Tou Jinfa;Tang Weibing;Lyu Shangyao;Li Wen;Huang Yumei;Qi Zhenghong;Zheng Shan(Department of Pediatric Surgery,Children's Hospital of Fudan University and Shanghai Key Laboratory of Birth Defect,Shanghai 201102,China;WuXi Diagnostics Innovation Research Institute,Shanghai 200131,China;Department of Hepatology,Children's Hospital of Fudan University,Shanghai 201102,China;Department of Pediatric Surgery,Xiamen Children's Hospital,Xiamen 361006,China;Department of Pediatric Surgery,Shanxi Children's Hospital,Taiyuan 030013,China;Department of Pediatric Surgery,Children's Hospital,Zhejiang University School of Medicine,Hangzhou 310057,China;Department of Pediatric Surgery,Nanjing Children's Hospital,Nanjing 210008,China;Department of Pediatric Surgery,Hainan Children's Hospital,Haikou 571103,China;Department of Neonatology,Qilu Hospital,Shandong University,Jinan 250012,China;Department of Neonatology,Second Affiliated Hospital,Wenzhou Medical University,Wenzhou 325088,China)

机构地区：[1]复旦大学附属儿科医院外科,上海市出生缺陷防治重点实验室,上海201102 [2]上海药明奥测医疗科技有限公司,上海200131 [3]复旦大学附属儿科医院肝病中心,上海201102 [4]厦门市儿童医院外科,厦门361006 [5]山西省儿童医院外科,太原030013 [6]浙江大学医学院附属儿童医院外科,杭州310057 [7]南京市儿童医院外科,南京210008 [8]海南省儿童医院外科,海口571103 [9]山东大学齐鲁医院新生儿科,济南250012 [10]温州医科大学附属第二医院新生儿科,温州325088 [11]杭州市儿童医院肝病感染科,杭州310005

出　　处：《中华小儿外科杂志》2023年第7期625-630,共6页Chinese Journal of Pediatric Surgery

基　　金：上海申康医院发展中心临床三年行动计划资助(SHDC2020CR2009A);上海市临床重点专科(shslczdzk05703)。

摘　　要：目的进一步验证血清MMP-7对胆道闭锁的诊断准确性,明确血清MMP-7在梗阻性黄疸鉴别诊断流程中的价值。方法前瞻性分析2020年6月至2021年5月复旦大学附属儿科医院、厦门市儿童医院等9家儿童医学中心收治的因梗阻性黄疸自愿要求检测血清MMP-7的患儿临床资料。根据手术探查结果或肝活检病理检查结果或保守治疗随访过程中黄疸消退与否为诊断标准,将患儿分为BA组(确诊胆道闭锁)及Non-BA组(排除胆道闭锁),比较两组血清MMP-7值差异。绘制受试者操作特征曲线及诊断四格表,计算灵敏度、特异度等。以复旦大学附属儿科医院为例,比较近年来胆道探查阴性率及Kasai手术年龄差异,采用Kruskal-Wallis检验比较不同时期的患儿手术日龄差异。结果符合纳入排除标准的患儿共217例,其中130例为BA组,87例为Non-BA组。BA组血清MMP-7中位浓度为60.10(37.00,97.94)ng/ml,Non-BA组为11.10(7.97,14.83)ng/ml,组间比较差异有统计学意义(Z=11.63,P<0.001)。血清MMP-7受试者操作特征曲线下面积为0.97(95%CI:0.94~0.99)。以血清MMP-7大于20 ng/ml为阳性绘制诊断四格表,诊断灵敏度92.31%(120/130,95%CI:85.95%~96.04%),特异度93.10%(81/87,95%CI:85.03%~97.17%),阳性预测值95.24%(120/126,95%CI:89.49%~98.05%),阴性预测值89.01%(81/91,95%CI:80.29%~94.32%)。复旦大学附属儿科医院自2020年6月加入血清MMP-7辅助诊断后,胆道探查阴性率10.2%(12/118)及Kasai手术日龄52(39,68)d均有下降。结论血清MMP-7在梗阻性黄疸诊断流程中有重要价值,其作为胆道闭锁诊断标志物具有较大的临床意义,可将其加入胆道闭锁术前辅助诊断,以降低胆道探查阴性率及提早行Kasai手术时间,改善预后。Objective To validate the diagnostic accuracy of serum matrix metalloproteinase-7(MMP-7)for biliary atresia(BA)and further evaluate its diagnostic value for obstructive jaundice(OJ).Methods For this multicenter prospective clinical trial,217 OJ infants at 9 domestic medical centers voluntarily requesting a detection of serum MMP-7 were recruited from June 2020 to May 2021.The serum concentration of MMP-7 was measured by an ELISA kit.The gold standard was surgical exploration,liver histology or jaundice clearance after conservative treatment.The differences of serum MMP-7 were compared between groups BA(n=130)and non-BA(n=87).Receiver operating characteristic(ROC)curve was plotted and sensitivity and specificity were calculated.Negative rate of surgical exploration and age of Kasai operation were summarized with the data from Children's Hospital of Fudan University by Kruskal-Wallis test.Results Among them,11 refusing further diagnosis and treatment were excluded from final analysis.The median serum levels of MMP-7 were 60.10(37.00,97.94)ng/ml for BA group and 11.10(7.97,14.83)ng/ml for non-BA group(Z=11.63,P<0.001).The area under the ROC curve(AUC)value was 0.97(95%CI:0.94,0.99).With a cutoff value of 20 ng/mL,serum MMP-7 achieved a diagnostic sensitivity of 92.31%(120/130;95%CI:85.95%-96.04%),specificity of 93.10%(81/87;95%CI:85.03%-97.17%),PPV of 95.24%(120/126;95%CI:89.49%-98.05%)and NPV of 89.01%(81/91;95%CI:80.29%-94.32%).The negative rate of surgical exploration(10.2%,12/118)and age of Kasai operation(52[39,68]d)declined after an addition of serum MMP-7.Conclusions Serum MMP-7 has a great diagnostic value for OJ.It should be added into routine preoperative BA tests to lower negative rate of surgical exploration and age of Kasai surgery.

关 键 词：胆道闭锁 金属基质蛋白酶 诊断 

分 类 号：R726.5[医药卫生—儿科]