S2408 Risk of Gastrointestinal Malignancies in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A US-Based Propensity Matched Cohort Study

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally and is increasingly linked to extrahepatic malignancies. While its association with hepatocellular carcinoma is well established, its role in gastrointestinal (GI) cancers remains underexplored. This study assessed the risk of site-specific gastrointestinal (GI) malignancies in patients with MASLD, including an age-stratified analysis across all cancer sites. Methods: We conducted a retrospective cohort study using TriNetX, a federated electronic health record network spanning 69 U.S. healthcare organizations. Adults (≥18 years) diagnosed with MASLD (International Classification of Diseases, Tenth Revision (ICD-10): K75.81, K76.0) between 2010–2020, confirmed by abdominal imaging, were included. Patients with viral hepatitis, alcohol-related liver disease, autoimmune hepatitis, HIV, solid organ transplant, or prior malignancy were excluded. Propensity score matching (1:1) was performed using demographic, metabolic, and clinical comorbidities to create well-balanced MASLD and non-MASLD cohorts (n = 360,650 each). Primary outcomes included incident esophageal, gastric, small intestinal, colorectal, gallbladder, and pancreatic cancers. Age-stratified analyses were performed within the MASLD cohort. Results: MASLD was independently associated with increased risk of colorectal (OR 1.20; 95% CI: 1.12–1.29), gastric (OR 1.34; 95% CI: 1.15–1.55), pancreatic (OR 1.36; 95% CI: 1.24–1.49), small intestinal (OR 1.26; 95% CI: 1.02–1.55), and gallbladder (OR 1.46; 95% CI: 1.22–1.75) cancers (all P < 0.05), with no significant association for esophageal cancer (OR 0.98; 95% CI: 0.82–1.18; P = 0.86). MASLD also conferred a 30% increased time-dependent risk of malignancy (HR 1.30; 95% CI: 1.29–1.31; P < 0.001). In age-stratified analysis, MASLD patients >50 years had significantly higher odds of gastric (OR 4.77; 95% CI: 3.28–6.94), colorectal (OR 4.69; 95% CI: 3.95–5.56), small intestinal (OR 3.43; 95% CI: 2.11–5.58), gallbladder (OR 4.05; 95% CI: 3.78–10.52), and pancreatic cancers (OR 8.61; 95% CI: 6.35–11.69) compared to those ≤50 (all P < 0.001). Conclusion: MASLD is independently associated with elevated risk of multiple GI malignancies, especially colorectal, pancreatic, and gallbladder cancers. The pronounced age-related risk gradient underscores the need for risk-adapted surveillance, repositioning MASLD as a systemic condition with meaningful oncologic implications.