Abstract
BACKGROUND: The association between Helicobacter pylori (H. pylori) infection and the development of Barrett's esophagus (BE) in patients with gastroesophageal reflux disease (GERD) remains controversial. This study aimed to assess the impact of BE among GERD patients with and without evidence of H. pylori using a large real-world dataset. METHODS: A retrospective cohort analysis was conducted using the TriNetX Global Collaborative Network comprising 147 healthcare organizations. Two cohorts of patients aged 18-50 years with GERD were identified: Cohort 1 (n=179,757), GERD patients with confirmed H. pylori infection, and Cohort 2 (n=179,757), GERD patients without H. pylori exposure. Propensity score matching was applied to balance demographics and comorbidities. The primary outcome was the diagnosis of BE (based on International Classification of Diseases, Tenth Revision (ICD-10): K22.7). Risk, survival, and incidence analyses were performed using measures of association, Kaplan-Meier curves, and t-tests. RESULTS: The incidence of BE was significantly higher in the GERD with H. pylori group (0.66%) compared to the GERD-only group (0.09%) (risk ratio (RR): 7.30, 95% CI: 6.20-8.60; p<0.001). Kaplan-Meier survival analysis demonstrated lower survival probability free of BE in the H. pylori cohort (97.84% vs 99.40%; log-rank p<0.001), with a hazard ratio (HR) of 7.13 (95% CI: 6.05-8.40; p=0.029). The number of BE instances was also significantly greater in the H. pylori cohort (mean: 3.15 vs. 1.67, p<0.001). CONCLUSIONS: Among young adults with GERD, concomitant H. pylori infection is associated with a significantly higher risk of developing BE. These findings challenge the previously held notion of a protective role of H. pylori and suggest the need for targeted surveillance in this subgroup.