Gallbladder Removal With 3-Plus Risk Factors May Increase MASLD Risk

Patients who undergo gallbladder removal face a 48% higher risk of developing metabolic dysfunction–associated steatotic liver disease (MASLD), and that risk more than quintuples if they already have 3 or more cardiometabolic risk factors (CMRFs), according to a nationwide cohort study from South Korea.1

Published in Scientific Reports, the study found that the combination of undergoing cholecystectomy and having multiple metabolic health issues sharply increased the likelihood of MASLD, a liver condition that can progress to metabolic dysfunction–associated steatohepatitis (MASH), cirrhosis, and liver cancer.1,2

“To the best of our knowledge, our large-scale longitudinal study is the first to demonstrate the temporal and causal relationship between cholecystectomy and new-onset MASLD,” the authors said.1

New findings underscore the importance of careful patient selection for gallbladder removal. | Image credit: Peakstock – stock.adobe.com

Researchers analyzed data from the 2009-2019 Korean National Health Insurance Service-National Sample Cohort, including 4664 patients who underwent cholecystectomy and 13,992 matched controls who did not. Over an average follow-up of 5.35 years, patients who had the surgery developed MASLD at a rate of 29.87 per 1000 person-years overall, compared with 20.37 per 1000 in the control group (HR, 1.48; 95% CI, 1.34-1.64).

Higher Risk With More CMRFs

The study also showed that having 3 or more CMRFs puts patients at a higher risk of MASLD regardless if they had their gallbladder removed or not. The reference group was patients with fewer than 3 CMRFs who did not undergo the surgery. In comparison, patients with ≥ 3 CMRFs faced a 345% higher risk of MASLD after undergoing surgery and a 194% higher risk if they did not, with incidence rates of 38.38 and 25.7 per 1000 person-years, respectively. Patients who underwent cholecystectomy with < 3 CMRFs had the lowest relative risk of MASLD, with a 22% increased risk compared with their peers who opted out of the surgery and an incidence rate of 10.55 per 1000 person-years.

In a fully adjusted model that accounted for interactions between surgery, age, sex, and body mass index, patients with cholecystectomy and ≥ 3 CMRFs faced a 426% increased risk of MASLD (adjusted HR, 5.26; 95% CI, 2.35-11.78) compared with the reference group. According to the authors, a synergistic effect between cholecystectomy and cardiometabolic risk factors could explain the increased risk of developing MASLD, underscoring the importance of careful patient selection for gallbladder removal.

“Moreover, if cholecystectomy is mandatory for individuals with three or more cardiometabolic risk factors, risk factors should be more aggressively managed to prevent MASLD development, and more frequent monitoring to detect its onset should be adopted in this group,” the researchers wrote. “In determining whether to perform cholecystectomy, clinicians should weigh the clinical balance between the potential development of MASLD associated with cholecystectomy and the complications of untreated gallbladder disease.”

It’s important to note the study relied on the fatty liver index (FLI) rather than liver biopsy, the current gold standard for diagnosing steatotic liver disease. While the FLI is a validated, noninvasive screening tool, the authors said it may lead to misclassification in borderline or transient cases, and no alternative thresholds or secondary definitions were applied. Although the analysis adjusted for multiple covariates, residual confounding from unmeasured metabolic factors cannot be ruled out, and these findings may have limited generalizability to populations beyond South Korea, warranting further research. Patients who underwent cholecystectomy may also have been subject to more frequent clinical monitoring, introducing potential surveillance bias, the authors noted.

References

1. Jeon HJ, Eun HS, Rou WS, Kim SH, Lee BS, Ahn SK. Association between cholecystectomy and the risk of new-onset metabolic dysfunction-associated steatotic liver disease: a risk-stratified cohort study. Sci Rep. 2025;15(1):28223. doi:10.1038/s41598-025-13556-5
2. Metabolic dysfunction-associated steatotic liver disease (MASLD). Cleveland Clinic. Updated November 3, 2024. Accessed August 12, 2025. https://my.clevelandclinic.org/health/diseases/22437-non-alcoholic-fatty-liver-disease