Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia

J Pediatr Gastroenterol Nutr. 2023 Jul 1;77(1):97-102. doi: 10.1097/MPG.0000000000003792. Epub 2023 Apr 19.

Abstract

Objectives: Matrix metallopeptidase-7 (MMP-7) and osteopontin (OPN) are important components in the pathophysiology of fibrosis in biliary atresia (BA). There has been much recent interest in MMP-7 serum level in the diagnosis of BA. We aimed to assess the diagnostic accuracy and prognostic value of both MMP-7 and OPN in a Western BA study.

Methods: Diagnostic value was assessed by comparison of serum MMP-7 and OPN levels in infants with BA and age-matched cholestatic controls. Prognostic value was assessed through subsequent clearance of jaundice (COJ) and need for liver transplantation (LT).

Results: Serum was assessed from 32 BA and 27 controls. Median MMP-7 was higher in BA (96.4 vs 35 ng/mL; P < 0.0001) with an optimal cut-off value of 69 ng/mL. Sensitivity and specificity was 68% and 93%, respectively [negative predictive value (NPV) = 71%]. Similarly, median OPN was higher in BA (1952 vs 1457 ng/mL; P = 0.0001) and an optimal cut-off of 1611 ng/mL. Sensitivity and specificity was 84% and 78%, respectively (NPV = 81%). MMP-7 level correlated positively with Ishak liver fibrosis score (r = 0.27, P = 0.04). Neither MMP-7 (70 vs 100 ng/mL; P = 0.2) nor OPN (1969 vs 1939 ng/mL; P = 0.3) were predictive of COJ, or need for LT (99 vs 79 ng/mL; P = 0.7, and 1981 vs 1899 ng/mL; P = 0.2), respectively.

Conclusions: MMP-7 and OPN may have contributory value in the diagnosis of BA, but remain far of the "gold standard" role. Much more prospective data are required and collaborative multi-center initiatives should be the next logical steps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biliary Atresia*
  • Biomarkers
  • Humans
  • Infant
  • Matrix Metalloproteinase 7
  • Osteopontin
  • Prospective Studies

Substances

  • Osteopontin
  • Matrix Metalloproteinase 7
  • Biomarkers