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

Abstract

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. Retrospective cohort study with 1:1 propensity score matching. Global, multicentre real-world analysis using deidentified electronic health records from over 130 healthcare organisations in the TriNetX Global Collaborative Network. 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 outcomes: Incidence of CRC and BCN. Combined incidence of CRC and BCN. Outcomes were assessed with and without controlling for metabolic risk factors using Cox proportional hazards models. 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. 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.