Liver fibrosis classification on trichrome histology slides using weakly supervised learning in children and young adults.

Background: Traditional liver fibrosis staging via percutaneous biopsy suffers from sampling bias and variable inter-pathologist agreement, highlighting the need for more objective techniques. Deep learning models for disease staging from medical images have shown potential to decrease diagnostic variability, with recent weakly supervised learning strategies showing promising results even with limited manual annotation. Purpose: To study the clustering-constrained attention multiple instance learning (CLAM) approach for staging liver fibrosis on trichrome whole slide images (WSIs) of children and young adults. Methods: This is an ethics board approved retrospective study utilizing 217 trichrome WSI from pediatric liver biopsies for model development and testing. Two pediatric pathologists scored WSI using two liver fibrosis staging systems, METAVIR and Ishak. Cases were then secondarily categorized into either high- or low-stage liver fibrosis and used for model development. The CLAM pipeline was used to develop binary classification models for histological liver fibrosis. Model performance was evaluated using area under the curve (AUC), accuracy, sensitivity, specificity, and Cohen's Kappa. Results: The CLAM models showed strong diagnostic performance, with sensitivities up to 0.76 and AUCs up to 0.92 for distinguishing low- and high-stage fibrosis. The agreement between model predictions and average pathologist scores was moderate to substantial (Kappa: 0.57-0.69), whereas pathologist agreement on the METAVIR and Ishak scoring systems was only fair (Kappa: 0.39-0.46). Conclusions: CLAM pipeline showed promise in detecting features important for differentiating low- and high-stage fibrosis from trichrome WSI based on the results, offering a promising objective method for liver fibrosis detection in children and young adults.