S2407 Risk of Non-Gastrointestinal Solid Organ Malignancy in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A US-based Propensity Matched Cohort Study

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), affecting over one-third of the global population by 2030, represents the most prevalent chronic liver condition worldwide. While MASLD's association with hepatocellular carcinoma is established, its relationship with extrahepatic malignancies remains poorly defined. We investigated the risk of overall and site-specific non-gastrointestinal cancers in MASLD patients using comprehensive real-world data. Methods: We conducted a retrospective cohort study using TriNetX, a federated electronic health record (EHR) network comprising 69 U.S. healthcare organizations. Adults (≥18 years) with MASLD were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes (K75.81, K76.0) between 2010–2020, with radiologic confirmation. Patients with alcohol-related liver disease, viral hepatitis, autoimmune liver disease, organ transplant, HIV, or prior malignancy were excluded. Propensity score matching (1:1) was performed for demographics, comorbidities, and smoking history, yielding matched cohorts (n = 360,650 each). Outcomes included overall and site-specific cancers (thyroid, breast, kidney, prostate, lung). Odds ratios (ORs) with 95% confidence intervals (CIs) and Kaplan-Meier analyses were performed. Results: MASLD patients demonstrated a significantly elevated malignancy risk compared to matched controls (OR 1.35; 95% CI: 1.33–1.36; P < 0.001). Site-specific analysis revealed increased risks for thyroid cancer (OR 1.32; 95% CI: 1.20–1.46), breast cancer (OR 1.17; 95% CI: 1.11–1.23), kidney cancer (OR 1.34; 95% CI: 1.24–1.46), and prostate cancer (OR 1.13; 95% CI: 1.07–1.20). Notably, lung cancer risk remained unchanged (OR 1.03; 95% CI: 0.97–1.09). Sex-stratified analysis revealed women experienced higher overall malignancy burden than men (24.5% vs 20.1%; OR 1.29; 95% CI: 1.27–1.32), with men showing predominant risks for prostate and kidney cancers. Conclusion: This large-scale analysis establishes MASLD as an independent risk factor for multiple extrahepatic malignancies, with a 35% increased overall cancer risk. The pronounced associations with hormone-sensitive cancers (thyroid, breast, prostate) and kidney cancer suggest shared metabolic pathways linking hepatic steatosis to carcinogenesis. These findings mandate comprehensive cancer surveillance strategies in MASLD patients, particularly women, and highlight the systemic nature of metabolic dysfunction beyond hepatic manifestations.