Diagnostic Accuracy of a Capsule Sponge Trefoil Factor 3 Test for Barrett’s Esophagus in Patients with Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis

Introduction: Current guidelines suggest swallowable capsule-sponge devices with biomarkers can be used as alternatives to endoscopy for detecting Barrett’s Esophagus (BE) in at-risk patients. We analyzed the screening performance of capsule-sponge with Trefoil-Factor-3 (TFF3) in patients with symptomatic acid reflux and assessed test performance across individual risk factors. Methods: The study protocol was registered in PROSPERO (CRD420250652091). Eligible studies reported results for both capsule-sponge-TFF3 and endoscopic assessment in adults with reflux symptoms and no history of BE. A systematic search was conducted through August 29, 2025. Two reviewers independently screened and extracted data using COVIDENCE. Risk of bias was assessed via QUADAS-2. Sensitivity and specificity were estimated in SAS v9.4 using bivariate mixed models allowing estimation of likelihood ratios, diagnostic odds ratios, and predictive values; meta-regression models were estimated for individual risk factors, acid suppressant use and BE prevalence. Results: We identified six studies involving 1,454 participants in our meta-analysis. Pooled sensitivity for BE was 0.87 (95% CI: 0.80–0.94), specificity was 0.88 (95% CI: 0.80–0.95), negative predictive value at 20% prevalence was 0.96 (95% CI: 0.95–0.98), and the diagnostic odds ratio was 47.82 (95% CI: 44.99–50.83). Smoking and acid suppressant use were associated with increased specificity. Discussion: Overall, our findings show that capsule-sponge-TFF3 is an effective minimally invasive screening tool for patients at risk of BE. Increased specificity in smokers may help reduce unnecessary endoscopies in this higher-risk group.