Lean individuals with metabolic-dysfunction associated steatotic liver disease and gastrointestinal cancers risk: A retrospective cohort study.

811 Background: Lean individuals with MASLD may represent a distinct subgroup at increased risk for gastrointestinal cancers, though evidence from real-world data remains limited. This study aimed to investigate the association between lean MASLD and GI cancer incidence using a large, multicenter retrospective cohort. Methods: We performed a population-based retrospective cohort study utilizing the TriNetX network, which compiles de-identified electronic health records from healthcare institutions across the United States. Patients with MASLD were classified as lean or non-lean (BMI ≥ 25) and were compared accordingly. The primary outcomes were gastrointestinal cancers and their subtypes, evaluated over a 5-year follow-up period using Cox proportional hazards models. Results: After 1:1 propensity score matching on demographics, comorbidities, labs, and medication use, 34,663 patients remained in each group with comparable characteristics. Over 5 years, lean individuals with MASLD exhibited significantly higher incidence of overall GI cancer compared to non-lean individuals (2.2% vs. 1.4%; HR 1.66, 95% CI: 1.48–1.87). Elevated risks were observed for esophageal cancer (HR 3.00, 95% CI: 1.80–4.99), gastric cancer (HR 2.96, 95% CI: 2.00–4.37), pancreatic cancer (HR 2.55, 95% CI: 2.00–3.26), colorectal cancer (HR 1.53, 95% CI: 1.13–2.06), biliary tract cancer (HR 1.76, 95% CI: 1.16–2.67), and unspecified GI cancers (HR 2.03, 95% CI: 1.17–3.53). Liver cancer rates were similar between groups (HR 1.05, 95% CI: 0.85–1.31). Conclusions: Lean MASLD was associated with a significantly increased risk of several gastrointestinal cancers, underscoring the need for tailored cancer surveillance strategies in this vulnerable subgroup. 5-year incidence of clinical outcome in lean and non-lean metabolic dysfunction-associated steatotic liver disease. Outcome MASLD leanEvents N (%) MASLD non-leanEvents N (%) Hazard Ratio (95% CI) p-value Gastrointestinal cancer 709 (2.2%) 455 (1.4%) 1.66 (1.48−1.87)