Pancreatic cancer risk and metastatic outcomes in patients with metabolic dysfunction–associated steatotic liver disease.

Abstract

e16440 Background: Pancreatic cancer (PC) is a malignancy with poor survival outcomes. Metabolic dysfunction–associated steatotic liver disease (MASLD) may influence PC risk and progression; however, its association with incidence, metastatic patterns, and clinical outcomes is unclear. Methods: We conducted a retrospective cohort study using the TriNetX Research Network from 2010 to 2026, including adults with MASLD and PC. Patients with other chronic liver diseases were excluded. First, two cohorts were established: patients with MASLD and patients without MASLD. Incidence rates of PC were calculated for each cohort. The MASLD and non-MASLD cohorts were then propensity score–matched in a 1:1 ratio to evaluate the risk of developing PC after 5 years. Subsequently, among patients diagnosed with PC, individuals were stratified into MASLD and non-MASLD groups and again matched 1:1 to compare metastatic outcomes after 1 and 2 years. Analyses were performed using Cox proportional hazards regression models and hazard ratios (HRs) with 95% confidence intervals. Results: 65,857 patients with MASLD and 333,116 without MASLD were included. The incidence of PC was 520 cases per 100,000 in the MASLD cohort compared with 250 cases per 100,000 in the non-MASLD cohort, with incidence rates of 4.3×10⁻⁴ and 2.4×10⁻⁴ cases per person-year, respectively. After matching 62,941 patients per group, MASLD was associated with a higher risk of PC compared with non-MASLD individuals (HR, 1.47; 95% CI, 1.17–1.86; p = 0.001). Among patients with PC, 10,526 patients with MASLD were matched 1:1 to non-MASLD patients. MASLD was associated with a higher risk of metastatic disease within 1 year (HR, 1.06; 95% CI, 1.01–1.11; p = 0.024), with an increased risk of peritoneal carcinomatosis (HR, 1.15; 95% CI, 1.03–1.28; p = 0.010). Risks were similar for liver metastasis (HR, 1.00; 95% CI, 0.94–1.07; p = 0.93), lung metastasis (HR, 1.07; 95% CI, 0.96–1.20; p = 0.25), bone metastasis (HR, 0.87; 95% CI, 0.75–1.00; p = 0.05), and brain metastasis (HR, 0.85; 95% CI, 0.65–1.13; p = 0.25). Over 2 years, MASLD remained associated with higher rates of peritoneal carcinomatosis (HR, 1.22; 95% CI, 1.10–1.35; p < 0.0001) and lung metastasis (HR, 1.13; 95% CI, 1.02–1.24; p = 0.02). Liver metastasis (HR, 1.04; 95% CI, 0.98–1.10; p = 0.17), bone metastasis (HR, 0.92; 95% CI, 0.81–1.05; p = 0.21), and brain metastasis (HR, 0.85; 95% CI, 0.66–1.10; p = 0.23) were similar between groups. Conclusions: MASLD is associated with a higher risk of incident PC and with an increased metastatic burden, particularly involving peritoneal and lung spread. These findings highlight MASLD as an important risk in PC and underscore the need for further mechanistic and prospective studies to clarify its role in pancreatic carcinogenesis and disease progression.