Influence of MASLD and MAFLD on long‐term extrahepatic cancer incidence and cancer mortality in regional Australia

Background and Aims Metabolic (dysfunction)‐associated steatotic liver disease (MASLD) has been linked to an increased risk of extrahepatic cancers. Whether MASLD or metabolic (dysfunction)‐associated fatty liver disease (MAFLD) is associated with an increased risk of extrahepatic cancer incidence or death in Australia is unknown. Methods This was a study from the Crossroads 1 cohort, enrolling randomly selected adults from regional Australia between 2001 and 2003 to partake in a comprehensive evaluation of health. MASLD is defined as fatty liver index (FLI) ≥60, one metabolic risk factor and no alternate liver disease, while MAFLD was defined as FLI ≥60 with overweight/obesity, type 2 diabetes mellitus (T2DM) and/or metabolic dysfunction. Longitudinal outcomes linked through cancer registry, hospital admission and death registry datasets and defined according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. Results In total, 1324 and 1444 participants respectively are included in the MASLD and MAFLD analyses. Prevalence was 35.4% (MASLD) and 40.7% (MAFLD). Median follow‐up time was 19.7 years (interquartile range 19.1–20.1). Neither form of fatty liver disease (FLD) was associated with an increased risk of death related to extrahepatic cancer compared to those without FLD. Both forms of FLD were associated with an increased incidence of colorectal cancer (MASLD adjusted sub‐hazard ratio (sHR) 2.90, 95% CI 1.17–7.17; MAFLD: sHR 3.15, 95% CI 1.43–6.96) following adjustment for confounding factors. This was primarily influenced by a difference seen among females (sHR 3.89–4.32). Conclusion Neither MASLD nor MAFLD was associated with an increased risk of extrahepatic cancer‐related death, but they were associated with an increased risk of colorectal cancer incidence, particularly among females.