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Both nonalcoholic fatty liver disease and metabolic dysfunction–associated fatty liver disease, especially with fibrosis, increase colorectal cancer risk.

“Nonalcoholic fatty liver disease (NAFLD) often carries metabolic dysfunction such as type 2 diabetes mellitus (T2DM) and obesity, which are significantly associated with increased risks of cardiovascular events and cancers,” researchers wrote in Clinical and Translational Gastroenterology. “Extrahepatic malignancy is the second leading cause of death, after cardiovascular disease, among patients with NAFLD. In a recent T2DM cohort study, NAFLD was an independent risk factor for mortality from any type of malignancy.”

Colorectal cancer (CRC) is one of the most common malignancies throughout the world, the researchers noted, and CRC and NAFLD have common risk factors, including obesity, metabolic syndrome, and diabetes. However, the association between NAFLD and CRC remains unclear.

The study team hypothesized that metabolic dysfunction–associated fatty liver disease (MAFLD)—the new definition based on the presence of metabolic dysfunction among people with fatty liver—would have a stronger association with CRC than conventional NAFLD. They analyzed data for more than 8.9 million adults aged 40 to 64 years from a nationwide health screening database. Participants were separated by the presence of FLD criteria into four groups: neither NAFLD nor MAFLD, NAFLD only, MAFLD only, or both NAFLD and MAFLD.

Among participants, 28.2% met the criteria for NAFLD, 37.4% met the criteria for MAFLD, and 27.6% met the criteria for both NAFLD and MAFLD.

CRC Incidence

Over a median follow-up of 10.1 years, 60,888 patients were diagnosed with CRC, according to the study findings.

“The CRC incidence rate was 85.7 per 100,000 person-years in participants with NAFLD and 63.2 per 100,000 person-years in participants without NAFLD. The incidence rate was 89.9 per 100,000 person-years in those with MAFLD and 57.5 per 100,000 person-years, without MAFLD,” researchers wrote. “The cumulative CRC incidence was higher in participants with FLD by either definition than in those without FLD.”

Impact of NAFLD and MAFLD

NAFLD and MAFLD were individually, and together, linked with a significantly increased risk of CRC, the study showed. Multivariable-adjusted hazard ratios for CRC were 1.32 with MAFLD only, 1.18 with both NAFLD and MAFLD, and 1.16 with NAFLD only compared with no FLD. Advanced liver fibrosis further elevated CRC risk for each FLD type.

The researchers wrote that “this is the first study to elucidate the association between MAFLD, by the new definition, and the risk of CRC development. As CRC is associated with metabolic abnormalities (eg, central obesity, metabolic syndrome, and diabetes), which are diagnostic features of MAFLD, it is reasonable that the new MAFLD criteria identify more accurately fatty liver associated with a high CRC risk.”