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.