FIB-4plus Score: A novel machine learning-based tool for screening high-risk varices in compensated cirrhosis (CHESS2004): An international multicenter study

A large percentage of patients undergoing esophagogastroduodenoscopy (EGD) screening do not have esophageal varices (EV) or have only small EV. We evaluated a large, international, multicenter cohort to develop a novel score, termed FIB-4plus, by combining the fibrosis-4 (FIB-4) score, liver stiffness measurement (LSM), and spleen stiffness measurement (SSM) to identify high-risk EV (HRV) in compensated cirrhosis. This international cohort study involved patients with compensated cirrhosis from 17 Chinese hospitals and one Croatian institution (NCT04546360). Two-dimensional shear wave elastography-derived LSM and SSM values, and components of the FIB-4 score (i.e., age, aspartate aminotransferase, alanine aminotransferase, and platelet count [PLT]) were combined using machine learning algorithms (logistic regression [LR] and extreme gradient boosting [XGBoost]) to develop the LR-FIB-4plus and XGBoost-FIB-4plus models, respectively. Shapley Additive exPlanations method was used to interpret the model predictions. We analyzed data from 502 patients with compensated cirrhosis who underwent EGD screening. The XGBoost-FIB-4plus score demonstrated superior predictive performance for HRV, with an area under the receiver operating characteristic curve (AUROC) of 0.927 (95% CI: 0.897-0.957) in the training cohort (n=268), and 0.919 (95% CI: 0.843-0.995) and 0.902 (95% CI: 0.820-0.984) in the first (n=118) and second (n=82) external validation cohorts, respectively. Additionally, the XGBoost-FIB-4plus score exhibited high AUROC values for predicting EV across all cohorts. The FIB-4plus score outperformed the individual parameters (LSM, SSM, PLT, and FIB-4). The FIB-4plus score effectively predicted EV and HRV in patients with compensated cirrhosis, providing clinicians with a valuable tool for optimizing patient management and outcomes.