Serum Transforming Growth Factor-β, Matrix Metalloproteinase-7, and Acoustic Radiation Force Impulse Elastography for Staging Liver Fibrosis in Children with Biliary Atresia: A Cross-Sectional Study

Abstract

Introduction: Biliary atresia (BA) is the leading cause of pediatric cholestatic liver disease and liver transplantation, and its prognosis is driven by hepatic fibrosis. Liver biopsy remains the reference standard for fibrosis staging but is invasive, underscoring the need for noninvasive alternatives. This study evaluated the association between serum levels of transforming growth factor-β (TGF-β) and matrix metalloproteinase-7 (MMP-7) and acoustic radiation force impulse (ARFI) elastography with the histological fibrosis stage in children with BA.​

Methods: This cross-sectional study enrolled children with suspected BA-related cholestasis at a national tertiary referral hospital in Jakarta, Indonesia, between January and June 2023. Serum TGF-β and MMP-7 levels were measured using enzyme-linked immunosorbent assay, and liver stiffness was assessed using ARFI elastography. Fibrosis was staged using liver biopsy and the Laennec scoring system, and dichotomized as F2–F3 or F4.

Results: Fifteen patients (10 girls; median age, 5 months) were analyzed; six had F2–F3 and nine had F4 fibrosis. Median TGF-β was marginally higher in F4 than in F2–F3 (1.081 vs. 1.057 ng/mL; p = 0.77), and MMP-7 did not differ between the groups (p = 0.41). ARFI staging agreed with histology in 13 of 15 patients (86.7%; κ = 0.72; p = 0.011), yielding 88.9% sensitivity and 83.3% specificity for F4.

Conclusion: In pilot cohort, serum TGF-β and MMP-7 did not distinguish advanced from intermediate fibrosis, whereas ARFI elastography showed agreement with histology. ARFI is a minimally invasive tool for fibrosis staging in BA and warrants validation in cohorts.

Keywords: Biliary Atresia, Liver Fibrosis, Transforming Growth Factor-Β, Matrix Metalloproteinase-7, Acoustic Radiation Force Impulse, Laennec Score