Interpretable Machine Learning Models for Early Detection of Metabolic Dysfunction-Associated Steatotic Liver Disease Using Non-Invasive Routine Clinical and Laboratory Data.

Introduction: The purpose of this study was to develop and evaluate multiple interpretable machine learning models for the early detection of metabolic dysfunction-associated steatotic liver disease (MASLD) using non-invasive routine clinical and laboratory data, with magnetic resonance imaging proton density fat fraction (MRI-PDFF) as a quantitative reference standard, and to assess the feasibility of MRI-PDFF-calibrated risk stratification as a pre-screening approach in clinical settings. Materials and Methods: This retrospective study analyzed a de-identified cohort of 152 patients using routine clinical and laboratory data collected at Fu Jen Catholic University Hospital (FJUH), Taiwan. A total of 17 routinely available clinical and anthropometric variables were used to develop and compare across ten interpretable machine learning models, with MRI-PDFF serving as the quantitative reference standard. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1-score. Model interpretability was assessed using Shapley Additive Explanations (SHAP) at both the patient and feature levels. Results: Logistic Regression demonstrated the highest discriminative performance (AUC = 0.873). Random Forest achieved the best overall classification performance, with an accuracy of 0.816, precision of 0.803, recall of 0.814, and an F1-score of 0.807. SHAP analysis identified the Hepatic Steatosis Index (HSI), body fat composition, age, and triglycerides (TG) as the dominant contributors to MASLD risk prediction. Conclusion: This study demonstrates that an interpretable, MRI-PDFF-calibrated machine learning approach based on routinely available, non-invasive clinical data is feasible for MASLD risk stratification. Both transparent linear models and ensemble methods showed clinically meaningful performance, while SHAP analysis highlighted key metabolic and anthropometric factors contributing to risk. This approach may assist in prioritizing individuals for further imaging evaluation in clinical practice.