INTRODUCTION: Non-invasive colorectal cancer (CRC) screening offers an important opportunity to increase colonoscopy participation and reduce mortality. This study evaluates the potential of the gut-liver axis to predict colorectal neoplasia using artificial intelligence (AI)-based analysis of the liver in routine CT images as an opportunistic screening approach. METHODS: In this retrospective study, data from 1,997 patients were analyzed, including 1,189 without neoplasia and 808 with colorectal neoplasia (423 adenomas, 385 CRC). Radiomic features were extracted from three-dimensional liver segmentations, and the dataset was split into training (n = 1,397) and test (n = 600) cohorts. Five machine learning models were trained using five-fold cross-validation on the 20 most informative features. RESULTS: The best-performing radiomics-based XGBoost model achieved a test AUROC of 0.810 (95% CI: 0.767-0.837), outperforming a clinical-only model (AUROC: 0.457). After threshold optimization, sensitivity reached 74.1% and specificity 72.3% for detecting colorectal neoplasia. Subclassification between CRC and adenoma was less accurate (AUROC: 0.674). DISCUSSION: These findings demonstrate that AI-based liver analysis from routine CT scans can predict colorectal neoplasia, supporting its potential as an accessible adjunct to CRC screening and highlighting the gut-liver axis as a novel biomarker source.
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