Serum Trefoil Factor 3 as a Potential Noninvasive Marker of Disease Activity and Endoscopic Remission in Ulcerative Colitis: A Prospective Longitudinal Study

Background/Objectives: Endoscopy is an invasive and expensive tool for evaluating ulcerative colitis (UC). Noninvasive biomarkers may complement endoscopy. Aim: To evaluate serum Trefoil Factor 3 (TFF3) as a potential noninvasive biomarker for UC activity and remission. Methods: This is a prospective longitudinal observational study including patients with UC. Disease activity was assessed by the Lichtiger Clinical Activity Index (LCAI) and UC Endoscopic Index of Severity (UCEIS). Clinical and endoscopic remission were defined as LCAI ≤ 3 and UCEIS ≤ 1, respectively. Serum TFF3 and fecal calprotectin were measured to evaluate the within-patient change in serum TFF3 from active disease to remission. Results: Follow-up of 75 patients with active UC showed that TFF3 was significantly higher in active UC than in remission and controls (9.85 ± 2.17 vs. 5.66 ± 2.42 vs. 2.64 ± 0.99 ng/mL; p < 0.001). TFF3 correlated positively with LCAI, UCEIS, and fecal calprotectin (p < 0.001). In multivariable analysis, fecal calprotectin was independently associated with baseline TFF3 concentrations. TFF3 discriminated active disease from remission (AUC = 0.902; 95% CI 0.869–0.936, patient-level cluster bootstrap), with 88.0% sensitivity and 73.3% specificity at an exploratory Youden-optimal cutoff of >7.27 ng/mL derived in the same cohort. Fecal calprotectin had an AUC of 0.915 (95% CI 0.877–0.950; difference −0.013, 95% CI −0.049 to 0.026). Adding TFF3 to a calprotectin model increased the AUC only slightly (+0.016, 95% CI 0.001–0.038). Conclusions: In this two-center cohort, serum TFF3 was associated with clinical, endoscopic, and fecal calprotectin-based measures of disease activity and decreased after remission, although it remained higher than in healthy controls. TFF3 may be a possible complementary noninvasive biomarker, but it is not a replacement for endoscopic evaluation, and its cutoff requires external validation before clinical use.