Functional dyspepsia and risk of Barrett's esophagus and dysplasia: A propensity-matched multicenter retrospective cohort study.

Abstract

Background: Functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) exhibit substantial symptom overlap (40%-50%), and up to one-third of patients diagnosed with FD demonstrate pathologic acid exposure on objective testing. While GERD is a well-established risk factor for Barrett's esophagus (BE), the association between FD diagnosis and BE risk remains unexplored. Understanding this relationship is critical because FD is typically diagnosed symptomatically without routine objective reflux testing in clinical practice, potentially masking undiagnosed GERD or identifying shared pathophysiologic mechanisms. We hypothesized that patients diagnosed with FD demonstrate an elevated risk for BE and Barrett's-associated dysplasia compared to matched controls.

Aim: To investigate the association between FD diagnosis and the risk of BE and dysplasia.

Methods: This retrospective cohort study utilized the TriNetX Global Collaborative Network database. Patients diagnosed with FD (International Classification of Diseases, 10^th Revision code K30) between January 2006 and December 2022 were identified, and propensity-score matched 1:1 with controls based on demographics, comorbidities, and GERD diagnosis. The primary outcomes were the development of BE and Barrett's-associated dysplasia. Cox proportional hazards regression analysis was performed to calculate hazard ratios (HR) with 95% confidence intervals (CI). A sensitivity analysis was conducted to include patients with documented esophagoduodenoscopy during the study period.

Results: After PSM, 384267 patients were included in each cohort. Patients with FD demonstrated significantly higher risk for BE (HR: 1.900, 95%CI: 1.813-1.991), Barrett's associated dysplasia (HR: 3.568, 95%CI: 3.064-4.155), and esophageal cancer (HR: 1.649, 95%CI: 1.450-1.875). Sensitivity analysis confirmed the increased risk of BE and dysplasia but not esophageal cancer.

Conclusion: Patients diagnosed with FD demonstrate substantially elevated risk for BE and dysplasia. This association, whether reflecting undiagnosed GERD, shared pathophysiology, or both, identifies FD patients as a higher-risk population warranting consideration of objective reflux testing and selective endoscopic evaluation in appropriate clinical contexts.