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.