Early Prediction of Liver Cirrhosis Up to Three Years in Advance: A Machine Learning Study Benchmarking Against the FIB-4 Score

Objective: Develop and evaluate machine learning (ML) models for predicting incident liver cirrhosis one, two, and three years prior to diagnosis using routinely collected electronic health record (EHR) data, and to benchmark their performance against the FIB-4 score. Methods: We conducted a retrospective cohort study using de-identified EHR data from a large academic health system. Patients with fatty liver disease were identified and categorized into cirrhosis and non-cirrhosis cohorts based on ICD-9/10 codes. Prediction scenarios were constructed using observation and prediction windows to emulate real-world clinical use. Demographics, diagnoses, laboratory results, vital signs, and comorbidity indices were aggregated from the observation window. XGBoost models were trained for 1-, 2-, and 3-year prediction horizons and evaluated on held-out test sets. Model performance was compared with FIB-4 using area under the receiver operating characteristic curve (AUC). Results: Final cohorts included 3,043 patients for the 1-year prediction, 1,981 for the 2-year prediction, and 1,470 for the 3-year prediction. Across all prediction windows, ML models consistently outperformed FIB-4. The XGBoost models achieved AUCs of 0.81, 0.73, and 0.69 for 1-, 2-, and 3-year predictions, respectively, compared with 0.71, 0.63, and 0.57 for FIB-4. Performance gains persisted with longer prediction horizons, indicating improved early risk discrimination. Conclusions: Machine learning models leveraging routine EHR data substantially outperform the traditional FIB-4 score for early prediction of liver cirrhosis. These models enable earlier and more accurate risk stratification and can be integrated into clinical workflows as automated decision-support tools to support proactive cirrhosis prevention and management.