<i>Helicobacter pylori</i> infection is associated with the risk and phenotypes of cholelithiasis: A multi-center study and meta-analysis

BACKGROUND Helicobacter pylori (H. pylori ) is a prevalent pathogen associated with various diseases. Cholelithiasis is also a common condition. H. pylori infection has been identified in the biliary system, suggesting its potential involvement in biliary diseases. However, the specific role of H. pylori in the development of cholelithiasis remains inconclusive. AIM To investigate the potential association between H. pylori infection and the development of cholelithiasis. METHODS We performed a retrospective study in more than 70000 subjects in health examination center from 3 institutions in the middle, northern and eastern China, from October 2018 to December 2021, to explore the potential association between H. pylori and cholelithiasis through univariate and multivariate analysis. Meanwhile, the influence of H. pylori on biliary-related parameters was investigated. A comprehensive analysis of previous studies concerned about H. pylori and cholelithiasis was also executed. RESULTS In our multi-center study, H. pylori was positively associated with cholelithiasis [odds ratio (OR) = 1.103, 95% confidence interval (CI): 1.001-1.216, P = 0.049]. Furthermore, H. pylori patients had less total and direct bilirubin than uninfected patients, while the total cholesterol and low-density lipoprotein cholesterol were more in H. pylori -positive participants (P &lt; 0.05). In the published articles, the cohort studies indicated H. pylori was a risk factor of cholelithiasis (hazard ratio =1.3280, 95%CI: 1.1810-1.4933, P &lt; 0.0001). The pooled results of case-control and cross-sectional studies showed positive association between H. pylori and cholelithiasis in Asia (OR = 1.5993, 95%CI: 1.0353-2.4706, P = 0.034) but not in Europe (OR = 1.2770, 95%CI: 0.8446-1.9308, P = 0.246). Besides, H. pylori was related to a higher choledocholithiasis/cholecystolithiasis ratio (OR = 3.3215, 95%CI: 1.1034-9.9986, P = 0.033). CONCLUSION H. pylori is positively correlated with cholelithiasis, choledocholithiasis phenotype particularly, especially in Asia, which may be relevant to bilirubin/cholesterol metabolism. Cohort studies confirm an increased risk of cholelithiasis in H. pylori patients.