EXPRESS: Serum trefoil factor 2 in acute nonvariceal gastrointestinal bleeding: Association with bleeding location in a prospective cohort

BACKGROUND: Distinguishing upper from lower gastrointestinal bleeding guides diagnostic and therapeutic decisions but may be difficult from clinical presentation alone. Trefoil factor 2 (TFF-2) is predominantly expressed in the gastroduodenal mucosa and contributes to mucosal protection and repair. PURPOSE: To determine whether admission serum TFF-2 concentrations are elevated in acute gastrointestinal bleeding and whether, among patients with confirmed bleeding, TFF-2 can distinguish upper from lower gastrointestinal bleeding. STUDY TYPE: Prospective, single-center observational cohort study. POPULATION: A total of 136 adults, including 70 patients with confirmed nonvariceal upper gastrointestinal bleeding, 36 with lower gastrointestinal bleeding, and 30 outpatient controls.Assessment Techniques or Outcomes:Serum TFF-2 was measured by enzyme-linked immunosorbent assay at admission before treatment, transfusion, or intervention. The outcomes were between-group differences in TFF-2 concentrations and discrimination of upper gastrointestinal bleeding from lower gastrointestinal bleeding and controls. STATISTICAL TESTS: Kruskal-Wallis testing, age- and sex-adjusted log-linear regression with HC3 robust standard errors, and receiver operating characteristic analysis were used. RESULTS: Median serum TFF-2 concentrations were highest in upper gastrointestinal bleeding (2035.5 pg/mL), followed by lower gastrointestinal bleeding (1913.5 pg/mL) and controls (1731.3 pg/mL; p<0.001). After adjustment for age and sex, TFF-2 remained higher in upper than lower gastrointestinal bleeding (geometric mean ratio, 1.14; 95% CI, 1.05-1.24; p=0.001) and controls (1.19; 95% CI, 1.12-1.27; p<0.001), whereas lower gastrointestinal bleeding did not differ from controls. The area under the curve was 0.627 (95% CI, 0.519-0.735) for upper versus lower bleeding and 0.757 (95% CI, 0.665-0.850) for upper bleeding versus controls. A cutoff of 2471 pg/mL had 100% specificity but 28.6% sensitivity for an upper rather than lower source. CONCLUSION: Higher admission serum TFF-2 concentrations were associated with upper gastrointestinal bleeding, although their ability to distinguish upper from lower gastrointestinal bleeding was limited. Larger multicenter studies are needed to determine whether TFF-2 provides clinically useful information beyond routine assessment.