Fecal alpha 1-antitrypsin clearance as a marker of clinical relapse in patients with Crohn's disease of the distal ileum

Background: Crohn's disease (CD) shows a chronic relapsing course but no marker of relapse is currently available. However, fecal α1-antitrypsin (α1-AT) clearance (α1-ATCI) is an indicator of protein loss and increases during active inflammation. We assessed the usefulness of fecal α1-ATCI in predicting clinical relapse in patients with inactive ileal CD. Design: In a prospective longitudinal study, 26 patients with inactive ileal CD (Crohn's disease activity index (CDAI) < 150) (18 males, mean age 43 ± 10, range 23-58) were enrolled. Fecal α1-ATCI and concentration, daily stool weight and serum α1-AT were measured at baseline (visit 1), after 1 week (visit 2) and 3 weeks (visit 3) in 24/26 patients (two drop-outs) (short-term study). In six of these 26 patients, fecal α1-ATCI was also measured every 3 months for 1 year (long-term study). All patients were clinically assessed every 3 months for 1 year and every 6 months for 2 years. Ten healthy volunteers were tested as controls. Methods: Serum and fecal α1-AT concentration was quantified by radial immunodiffusion. Results: The median fecal α1-ATCI value at baseline was higher in inactive patients undergoing clinical relapse (CDAI > 200) in the next 6 months than in those remaining in remission at 6 months (P = 0.03). Fecal α1-ATCI showed a 75% sensitivity, 85% specificity, 50% positive predictive value and 94% negative predictive value in predicting CD relapse in the next 6 months. In the long-term follow-up, fecal α1-ATCI values increased at 12 months compared with both baseline and 6 month values (P = 0.005; P = 0.009). Fecal α1-ATCI was higher in patients with raised C-reactive protein (P = 0.039). Conclusions: Results from our study suggest that fecal α1-ATCI is an indicator of clinical relapse in patients with CD of the distal ileum under regular surveillance.