Metabolic Dysfunction-Associated Fatty Liver Disease Increases Colon Cancer Risk: A Nationwide Cohort Study

Introduction: The association between nonalcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) has been controversial. Using the new consensus-driven definition, we evaluated the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with the risk of developing CRC. Methods: From a nationwide health screening database, we included 8,933,017 participants (48.6% male) aged 40-64 years between 2009 and 2010. Participants were categorized by the presence of fatty liver disease (FLD)-NAFLD and MAFLD, separately-and by the combination of the 2 definitions: neither FLD, NAFLD only, MAFLD only, or both FLD. The primary outcome was the development of CRC. Results: Among the participants, 2,517,330 (28.2%) had NAFLD, and 3,337,122 (37.4%) had MAFLD, whereas 2,465,151 (27.6%) met both NAFLD and MAFLD definitions. Over a median follow-up period of 10.1 years, 60,888 new CRC cases developed. NAFLD and MAFLD were each associated with a significantly higher risk of developing CRC. When the neither FLD group was the reference, multivariable-adjusted hazard ratios (95% confidence interval) for CRC were 1.16 (1.06-1.28) in the NAFLD only group, 1.18 (1.16-1.20) in the both FLD group, and 1.32 (1.28-1.35) in the MAFLD only group. The presence of advanced liver fibrosis further increased CRC risk in each FLD group. Discussion: FLD was associated with a higher risk of CRC development. CRC risk was higher in the presence of MAFLD, especially when accompanied by liver fibrosis.ope