BA-ECM Score

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. Summary Background Data: 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 BA patients were retrieved from our pathology archives 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. Retrospective chart review was performed to correlate clinical characteristics with BA-ECM score. Results: BA-ECM score, a multi-dimensional fibrosis architecture score, was significantly higher for biopsies from listed patients compared to non-listed patients (35.9 vs. 22.9, * P <0.0001). High BA-ECM score was characterized by thick, patchy, irregular ECM, while 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 multi-dimensional BA-ECM score that could be used to prognosticate disease course for BA patients.