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血清基质金属蛋白酶-7作为先天性心脏病胆汁淤积婴儿生物标志物的效用

Utility of Serum Matrix Metalloproteinase-7 as a Biomarker in Cholestatic Infants with Congenital Heart Disease.

作者信息

Pandurangi Sindhu, Kim Michael E, Noriega Nicolas, Conant Bradley, Seo JangDong, Mourya Reena, Shivakumar Pranavkumar, Peters Anna L, Misfeldt Andrew, Chlebowski Meghan

机构信息

University of Texas Southwestern Medical Center.

The Hospital for Sick Children.

出版信息

Res Sq. 2024 Oct 18:rs.3.rs-5004969. doi: 10.21203/rs.3.rs-5004969/v1.

DOI:10.21203/rs.3.rs-5004969/v1
PMID:39483898
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11527211/
Abstract

BACKGROUND

Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH.

METHODS

This is a single center cross sectional study including infants <180 days of age with cholestasis and serum MMP-7 levels collected from 2019-2023. Demographic data and descriptive statistics were summarized with medians with interquartile ranges and frequencies with percentages. Median MMP-7 levels were assessed via Wilcoxon rank-sum test.

RESULTS

A total of 149 patients were included. Patients with CHD had significantly elevated MMP-7 levels relative to the non-CHD cohort (50 vs. 34 ng/mL, p=0.009). Sub-analysis comparing infants with and without PH revealed significantly elevated median MMP-7 levels in those with clinically significant PH (125 vs. 39 ng/mL, p=0.010). CHD patients with PH had greater median MMP-7 compared to CHD patients without PH (154 vs 43 ng/mL, p=0.028).

CONCLUSIONS

Serum MMP-7 levels in infants with CHD-C were significantly elevated compared to those with cholestasis alone. MMP-7 may help identify non-BA cholestatic infants who have concurrent clinically significant pulmonary hypertension. Larger, prospective studies are needed to validate this finding and establish CHD-specific MMP-7 cutoffs.

摘要

背景

基质金属蛋白酶7(MMP-7)是诊断胆道闭锁(BA)的一种新型生物标志物,BA是婴儿期最常见的胆汁淤积性肝病。迫切需要确定先天性心脏病(CHD)婴儿中MMP-7水平的效用,以避免在这一高危人群中进行不必要的侵入性诊断程序。我们研究了MMP-7在区分CHD婴儿的BA与非BA胆汁淤积中的效用,以及临床显著肺动脉高压(PH)患儿中是否存在MMP-7升高。

方法

这是一项单中心横断面研究,纳入了2019年至2023年收集的年龄<180天、患有胆汁淤积且有血清MMP-7水平的婴儿。人口统计学数据和描述性统计用中位数及四分位间距和频率及百分比进行总结。通过Wilcoxon秩和检验评估MMP-7中位数水平。

结果

共纳入149例患者。与非CHD队列相比,CHD患者的MMP-7水平显著升高(50 vs. 34 ng/mL,p=0.009)。对有和无PH的婴儿进行亚分析显示,临床显著PH患儿的MMP-7中位数水平显著升高(125 vs. 39 ng/mL,p=0.010)。与无PH的CHD患者相比,有PH的CHD患者的MMP-7中位数更高(154 vs 43 ng/mL,p=0.028)。

结论

与单纯胆汁淤积婴儿相比,CHD-C婴儿的血清MMP-7水平显著升高。MMP-7可能有助于识别并发临床显著肺动脉高压的非BA胆汁淤积婴儿。需要更大规模的前瞻性研究来验证这一发现并确定CHD特异性的MMP-7临界值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7885/11527211/7cf80c475ff1/nihpp-rs5004969v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7885/11527211/120276003097/nihpp-rs5004969v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7885/11527211/082e38f5bb53/nihpp-rs5004969v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7885/11527211/7cf80c475ff1/nihpp-rs5004969v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7885/11527211/120276003097/nihpp-rs5004969v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7885/11527211/082e38f5bb53/nihpp-rs5004969v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7885/11527211/7cf80c475ff1/nihpp-rs5004969v1-f0004.jpg

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本文引用的文献

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Biliary atresia.先天性胆道闭锁。
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2
Fontan-Associated Liver Disease: A Review.法洛四联症相关肝病:综述
Cardiol Rev. 2024 Mar 13. doi: 10.1097/CRD.0000000000000684.
3
Diagnostic accuracy of serum matrix metalloproteinase-7 as a biomarker of biliary atresia in a large North American cohort.血清基质金属蛋白酶-7作为一种生物标志物对北美大样本队列胆道闭锁的诊断准确性。
Hepatology. 2024 Jul 1;80(1):152-162. doi: 10.1097/HEP.0000000000000827. Epub 2024 Mar 6.
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Conjugated hyperbilirubinemia is associated with increased morbidity and mortality after neonatal heart surgery.结合胆红素血症与新生儿心脏手术后发病率和死亡率的增加有关。
Cardiol Young. 2024 May;34(5):1083-1090. doi: 10.1017/S1047951123004158. Epub 2023 Dec 18.
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Cardiac complications caused by biliary diseases: A review of clinical manifestations, pathogenesis and treatment strategies of cholecardia syndrome.胆道疾病相关的心脏并发症:胆心综合征的临床表现、发病机制及治疗策略的综述。
Pharmacol Res. 2024 Jan;199:107006. doi: 10.1016/j.phrs.2023.107006. Epub 2023 Nov 23.
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Circulating biomarkers of extracellular matrix dysregulation are associated with adverse post-stage 2 outcomes in infants with single ventricle heart disease.细胞外基质失调的循环生物标志物与单心室心脏病婴儿 2 期后不良结局相关。
Sci Rep. 2023 Sep 28;13(1):16318. doi: 10.1038/s41598-023-43562-4.
7
Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia.基质金属蛋白酶-7 和骨桥蛋白血清水平作为胆道闭锁的生物标志物。
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8
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