Cholelithiasis and cholecystectomy increase the risk of gastroesophageal reflux disease and barrett's esophagus: evidence from meta-analysis and mendelian randomization analysis

Abstract Background Cholelithiasis or cholecystectomy is associated with bile reflux and may potentially contribute to the development of gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC); however, current observational studies yield inconsistent findings. Methods A search of literature until 3 November 2023 was done in PubMed, Web of Science, and Embase. Meta-analysis of observational studies assessing correlations between cholelithiasis or cholecystectomy and GERD, BE, and EAC risk factors were conducted. Mendelian randomization (MR) was then employed to assess the causative impact of genetic pre-disposition for cholelithiasis or cholecystectomy on these esophageal diseases. Results The results of the Meta-analysis indicated that cholelithiasis was significantly linked to an elevated risk in the incidence of BE (OR, 1.77; 95% CI, 1.37–2.29; p < 0.001) and cholecystectomy was a risk factor of GERD (OR, 1.37; 95%CI, 1.09–1.72; p = 0.008). We observed significant genetic associations between cholelithiasis and both GERD (OR, 1.06; 95% CI, 1.02–1.10; p < 0.001) and BE (OR, 1.21; 95% CI, 1.11–1.32; p < 0.001), as well as a correlation between cholecystectomy and both GERD (OR, 1.04; 95% CI, 1.02–1.06; p < 0.001) and BE (OR, 1.13; 95% CI, 1.06–1.19; p < 0.001). After adjusting for common risk factors, such as smoking, alcohol consumption and BMI in multivariate analysis, these variables still increase the risk of GERD and BE. Conclusions Our findings suggest that patients with cholelithiasis, regardless of whether they have undergone cholecystectomy or not, should prioritize the prevention and management of esophageal disorders.