Metabolic dysfunction-associated steatotic liver disease is a risk factor for gallstones: A multicenter cohort study

Aim: Gallstone formation is associated with metabolic dysfunction. Recently, new definitions of steatotic liver disease (SLD) have been proposed, including metabolic dysfunction-associated SLD (MASLD) and moderate alcohol intake (MetALD). We investigated the effects of MASLD/MetALD on gallstone formation. Methods: This multicenter observational cohort study enrolled 8766 consecutive health-check examinees who underwent abdominal ultrasonography between 2008 and 2021 (total observation period 39,105.9 person-years). All patients were classified into non-SLD, MASLD, or MetALD groups. The effect of MASLD on gallstone development was evaluated using multivariate Cox regression analysis. Results: Age, male sex, and MASLD were identified as independent risk factors for gallstone development. MASLD was associated with a significantly higher risk of developing gallstones than non-SLD (hazard ratio [HR] 1.7112; 95% confidence interval [CI] 1.4294-2.0486; p < 0.0001) and MetALD (HR 1.3516, 95% CI 1.0130-1.8033, p = 0.0406). However, the risk of MetALD did not significantly differ between the SLD and non-SLD groups. Hypertension was the only significant independent cardiometabolic risk factor for gallstone development in the MASLD group (HR 1.4350, 95% CI 1.0545-1.9528; p = 0.0216). Random forest analysis and directed acyclic graphs identified hypertension as the most important direct factor affecting gallstone development in patients with MASLD. Conclusions: MASLD was an independent risk factor for gallstone development, whereas MetALD presented a similar risk as non-SLD. Moderate alcohol consumption may reduce the risk of gallstone formation in patients with MASLD. Hypertension may be the most significant cardiometabolic risk factor for gallstone development in patients with MASLD.