Metabolic dysfunction-associated steatotic liver disease and colorectal neoplasms risk: a global propensity score-matched retrospective cohort study.

OBJECTIVES: To evaluate the association between metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic-associated steatohepatitis (MASH), and the risk of colorectal cancer (CRC) and benign colorectal neoplasms (BCN), and to explore whether liver fibrosis/cirrhosis modifies these associations. DESIGN: Retrospective cohort study with 1:1 propensity score matching. SETTING: Global, multicentre real-world analysis using deidentified electronic health records from over 130 healthcare organisations in the TriNetX Global Collaborative Network. PARTICIPANTS: Hospitalised adults aged 45-75 years between October 2019 and October 2024. Patients with prior diagnoses of colorectal neoplasia or other chronic liver diseases were excluded. Final matched cohorts included 138 902 MASLD and non-MASLD patients, 3715 MASH and non-MASH patients, and 1312 MASH patients with and without fibrosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes: Incidence of CRC and BCN. SECONDARY OUTCOME: Combined incidence of CRC and BCN. Outcomes were assessed with and without controlling for metabolic risk factors using Cox proportional hazards models. RESULTS: MASLD was associated with increased risks of CRC (HR 2.71, 95% CI 2.29 to 3.20) and BCN (HR 2.50, 95% CI 2.38 to 2.63), both p<0.001. MASH patients had a 5-fold higher risk of CRC (HR 5.03, 95% CI 1.43 to 17.72, p=0.005) and nearly 2-fold risk of BCN (HR 1.91, 95% CI 1.38 to 2.67, p<0.001). No significant differences in CRC or BCN risk were observed between MASH patients with versus without fibrosis/cirrhosis. CONCLUSIONS: MASLD and MASH are independent risk factors for CRC and BCN, irrespective of metabolic comorbidities. Fibrosis/cirrhosis does not significantly influence CRC risk. These findings support the need to revisit CRC screening guidelines for patients with MASLD/MASH. Further prospective studies are warranted to explore underlying mechanisms and evaluate preventative interventions.