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

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 to 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).

Conclusion: Serum MMP-7 levels in infants with congenital heart disease with cholestasis (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 cut-offs.