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Updated: May 21, 2025
Author Spotlight: Advancing Hepatic Fibrosis Diagnosis Using Magnetic Resonance Elastography and AI
Published on: July 21, 2023
Biliary Atresia-Extracellular Matrix Score: Automated Quantification of Liver Fibrosis Architecture in Biliary
Norah E Liang1,2, Jason L Guo1, Michelle F Griffin1
1Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA.
Objective:
To quantify liver fibrosis in infants with biliary atresia (BA) through automated analysis of collagen extracellular matrix (ECM) ultrastructure in index liver biopsies and use a composite fibrosis architecture score to predict native liver survival.
Background:
Despite early management with Kasai portoenterostomy, BA remains the leading indication for pediatric liver transplantation. There is no established method for quantitatively assessing liver fibrosis in patients with BA, and no factors to accurately predict which patients will ultimately require transplantation early versus late.
Methods:
Index liver biopsies from 12 patients with BA who underwent Kasai portoenterostomy at our institution were retrieved from our pathology archives. Liver biopsies from control patients without BA and with minimal liver fibrosis on biopsy were used as "Low Fibrosis Controls". Biopsies from BA patients who underwent upfront liver transplantation were used as "High Fibrosis Controls". Masson's trichrome-stained biopsies were scanned, tiled, binarized, and quantified for 147 ECM features. These features were reduced by Uniform Manifold Approximation and Projection. Pseudotime analysis was applied to summarize global variations in architecture and assign BA-ECM scores to all biopsy images in an unsupervised manner. A retrospective chart review was then performed to correlate clinical characteristics with BA-ECM score. BA-ECM scores were compared between BA patients who had been actively listed for liver transplantation during the study period and those who had not.
Results:
BA-ECM score, a multidimensional fibrosis architecture score, was significantly higher for biopsies from listed patients compared with non-listed patients (35.9 vs 22.9, * P < 0.0001). High BA-ECM score was characterized by thick, patchy, irregular ECM, whereas low BA-ECM score was associated with large-volume thin, porous collagen fibers. Survival analysis stratified by the third quartile BA-ECM score of all data points demonstrated a significant difference in native liver survival (* P = 0.02).
Conclusions:
We present the application of an automated ECM ultrastructure analysis tool designed to capture and quantify 147 aspects of fibrotic tissue heterogeneity. These manifold features are summarized using a multidimensional BA-ECM score that could be used to prognosticate disease course for patients with BA.
