Diagnostic accuracy of serum matrix metalloproteinase-7 as a biomarker of biliary atresia in a large North American cohort

胆道闭锁 生物标志物 医学 队列 内科学 胃肠病学 基质金属蛋白酶9 基质金属蛋白酶 生物 生物化学 移植 肝移植
作者
Sindhu Pandurangi,Reena Mourya,Shreya Nalluri,Fei Lin,Shun Dong,Sanjiv Harpavat,Stephen L. Guthery,Jean P. Molleston,Philip Rosenthal,Ronald J. Sokol,Kasper S. Wang,Vicky Ng,Estella M. Alonso,Evelyn Hsu,Saul J. Karpen,Kathleen M. Loomes,John C. Magee,Benjamin L. Shneider,Simon Horslen,Jeffrey Teckman,Jorge A. Bezerra
出处
期刊:Hepatology [Wiley]
被引量:1
标识
DOI:10.1097/hep.0000000000000827
摘要

Background and Aims: High levels of serum matrix metalloproteinase-7 (MMP-7) have been linked to biliary atresia (BA), with wide variation in concentration cutoffs. We investigated the accuracy of serum MMP-7 as a diagnostic biomarker in a large North American cohort. Approach and Results: MMP-7 was measured in serum samples of 399 infants with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays. The discriminative performance of MMP-7 was compared with other clinical markers. On the single-plex assay, MMP-7 generated an AUROC of 0.90 (CI: 0.87–0.94). At cutoff 52.8 ng/mL, it produced sensitivity = 94.03%, specificity = 77.78%, positive predictive value = 64.46%, and negative predictive value = 96.82% for BA. AUROC for gamma-glutamyl transferase = 0.81 (CI: 0.77–0.86), stool color = 0.68 (CI: 0.63–0.73), and pathology = 0.84 (CI: 0.76–0.91). Logistic regression models of MMP-7 with other clinical variables individually or combined showed an increase for MMP-7+gamma-glutamyl transferase AUROC to 0.91 (CI: 0.88–0.95). Serum concentrations produced by time resolved fluorescence energy transfer differed from single-plex, with an optimal cutoff of 18.2 ng/mL. Results were consistent within each assay technology and generated similar AUROCs. Conclusions: Serum MMP-7 has high discriminative properties to differentiate BA from other forms of neonatal cholestasis. MMP-7 cutoff values vary according to assay technology. Using MMP-7 in the evaluation of infants with cholestasis may simplify diagnostic algorithms and shorten the time to hepatoportoenterostomy.
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