An explainable machine learning model for prediction of high-risk nonalcoholic steatohepatitis

Early identification of high-risk metabolic dysfunction-associated steatohepatitis (MASH) can offer patients access to novel therapeutic options and potentially decrease the risk of progression to cirrhosis. This study aimed to develop an explainable machine learning model for high-risk MASH prediction and compare its performance with well-established biomarkers. Data were derived from the National Health and Nutrition Examination Surveys (NHANES) 2017-March 2020, which included a total of 5281 adults with valid elastography measurements. We used a FAST score ≥ 0.35, calculated using liver stiffness measurement and controlled attenuation parameter values and aspartate aminotransferase levels, to identify individuals with high-risk MASH. We developed an ensemble-based machine learning XGBoost model to detect high-risk MASH and explored the model's interpretability using an explainable artificial intelligence SHAP method. The prevalence of high-risk MASH was 6.9%. Our XGBoost model achieved a high level of sensitivity (0.82), specificity (0.91), accuracy (0.90), and AUC (0.95) for identifying high-risk MASH. Our model demonstrated a superior ability to predict high-risk MASH vs. FIB-4, APRI, BARD, and MASLD fibrosis scores (AUC of 0.95 vs. 0.50, 0.50, 0.49 and 0.50, respectively). To explain the high performance of our model, we found that the top 5 predictors of high-risk MASH were ALT, GGT, platelet count, waist circumference, and age. We used an explainable ML approach to develop a clinically applicable model that outperforms commonly used clinical risk indices and could increase the identification of high-risk MASH patients in resource-limited settings.