Gastrointestinal Cancer Risk in Steatotic Liver Diseases: MASLD, MetALD and ALD.

[BACKGROUND] Steatotic liver disease (SLD), which encompasses metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD) and alcohol-associated liver disease (ALD), is recognised as a risk factor for gastrointestinal cancers. However, the comparative risk of gastrointestinal cancers among MASLD, MetALD and ALD remains unclear.

[METHODS] We used a Japanese, nationwide, health insurance claims database between 2005 and 2024, encompassing approximately 10 million individuals and conducted a nationwide, population-based cohort study including 978,607 patients with MASLD, 366,152 with MetALD, 152,721 with ALD and 4,884,398 control individuals. The primary outcome was the incidence of gastrointestinal cancers, including hepatocellular carcinoma (HCC), biliary tract cancer, oesophageal cancer, gastric cancer, colorectal cancer and pancreatic cancer.

[RESULTS] Compared to controls, the adjusted hazard ratios (HRs) for HCC ranged from 3.55 to 5.39 across the MASLD, MetALD and ALD and from 1.45 to 1.66 for biliary tract cancer. The risks of both HCC and biliary tract cancer were significantly elevated in all SLD subgroups compared to controls. For oesophageal, gastric and colorectal cancers, the aHRs ranged from 0.75 to 1.26 in MASLD, from 1.09 to 1.44 in MetALD and from 1.13 to 2.48 in ALD, indicating increasing risk with greater alcohol consumption. The risk of pancreatic cancer was comparable to that in controls for both MetALD and ALD.

[CONCLUSIONS] Patients with SLD, including MASLD, MetALD and ALD, have a significantly higher risk of gastrointestinal cancers compared to the controls. The degree of risk varies according to the underlying liver disease subtype, particularly in relation to alcohol consumption. These findings underscore the importance of implementing risk-stratified cancer screening strategies in patients with SLD.