Journal Article

Serum matrix metalloproteinase-7 for discriminating biliary atresia: a diagnostic accuracy and validation study

Chen, Gong, Yan, Weili, Dong, Rui, Yang, Yifan, Xie, Xinbao, Du, Min, Zheng, Shan, Yang, Jingyun, Jiang, Jingying

2024

Overview

Background Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients. Methods This was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases ( n  = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients ( n  = 318, with 172 BA) and validated in a prospective cohort ( n  = 687, including 395 BA). Results The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946–0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5–97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0–90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9–93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6–96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0–30 days, which was 86.4% (95% CI: 75.0–94.0%), 95.5% (95% CI: 77.2–99.9%), 98.1% (95% CI: 89.7–100%), and 72.4% (95% CI: 52.8–87.3%), respectively. Conclusions The serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Biliary atresia / Biliary Atresia - blood / Biliary Atresia - diagnosis / Biological markers / Biomarker / Biomedical and Life Sciences / Biomedicine / Child, Preschool / Cholestasis / Cholestasis - blood / Cholestasis - diagnosis / Cutoff value / Diagnosis / Diagnosis, Differential / Diagnostic accuracy / Disease Biomarkers / Female / Health aspects / Humans / Infant / Infant, Newborn / Male / Matrix Metalloproteinase 7 - blood / Measurement / Medicine/Public Health / Neonate / Pediatric research / Prospective Studies / Proteases / Reproducibility of Results / Retrospective Studies / ROC Curve