Elevated LDL-c may warn of the risk of gallbladder stones in the patients with metabolic dysfunction-associated steatotic liver disease: A case-control study.

Purpose: This study aimed to explore the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and the development of new-onset gallbladder stone disease (GSD) and to identify factors that influence the occurrence of new-onset GSD in patients with MASLD.

Methods: In this retrospective case-control study, patients who underwent asymptomatic GSD screening during annual routine health check-ups at two hospitals in China between August 2017 and July 2022 were included. Patients with new-onset GSD and controls without GSD were matched 1:1 based on age, sex, race, occupation, diet, drinking habits, systolic blood pressure, diastolic blood pressure, and fasting blood glucose levels.

Results: The study comprised 1200 patients with new-onset GSD and 1200 controls without GSD. Patients with new-onset GSD had higher rates of MASLD (33.8% vs. 22.2 %, P < 0.001) and hypercholesterolemia (12.6% vs. 7.2 %, P < 0.001) compared to controls. Waist circumference (WC) (OR = 1.042, 95 % CI: 1.022-1.063, P < 0.001), high-density lipoprotein cholesterol (HDL-c) (OR = 0.048, 95 % CI: 0.037-0.062, P < 0.001), triglycerides (OR = 0.819, 95 % CI: 0.699-0.958, P = 0.013), and hypercholesterolemia (OR = 5.023, 95 % CI: 2.735-9.225, P < 0.001) were independently associated with new-onset GSD. Among patients with MASLD, WC (OR = 1.075, 95 % CI: 1.026-1.127, P = 0.003), total cholesterol (TC) (OR = 2.094, 95 % CI: 1.259-3.484, P = 0.004), HDL-c (OR = 0.088, 95 % CI: 0.054-0.142, P < 0.001), and low-density lipoprotein cholesterol (LDL-c) (OR = 4.056, 95 % CI: 2.669-6.163, P < 0.001) were independently associated with new-onset GSD.

Conclusions: The findings indicate that hypercholesterolemia is independently associated with GSD. Among patients with MASLD, hypercholesterolemia also showed an independent association with GSD. Notably, this study is the first to identify serum LDL-c levels as potentially the most significant risk factor for GSD, highlighting that elevated LDL-c could serve as an important indicator for individuals with MASLD.