Integrated Assessment of Intestinal Barrier Function and Microscopic Inflammation Using Confocal Laser Endomicroscopy for Relapse Prediction in Ulcerative Colitis

ABSTRACT Background Although the current strategy in ulcerative colitis (UC) focuses on achieving endoscopic healing to improve long‐term outcomes, patients with persistent microscopic inflammation or intestinal barrier dysfunction remain at increased risk of relapse. Objective We evaluated whether structural and functional abnormalities of the ileal and colonic mucosa assessed by probe‐based Confocal laser Endomicroscopy (pCLE) could predict the loss of therapeutic targets. Methods The prospective single‐center study included 81 UC patients in clinical and endoscopic remission monitored for 24 months. At baseline, barrier dysfunction and histological inflammation (HI) were assessed through colonoscopy with pCLE and targeted biopsies from the terminal ileum, ascending colon, sigmoid, and rectum. Clinical evaluations were performed every 3 months. Results The main predictors of loss of endoscopic remission were altered colonic permeability (Odds ratio OR = 3.85, 95% confidence interval CI 1.25–11.77, p = 0.018) and HI detected by pCLE (OR = 6.04, 95% CI 1.89–19.31, p = 0.002). Survival analysis demonstrated an increased risk of clinical relapse in patients with an altered barrier in the terminal ileum (Hazard ratio HR = 6.01, 95% CI 3.08–16.38, p 1) was significantly associated with unfavorable clinical outcome (HR = 3.39, 95% CI 1.23–8.38, p = 0.018). None of the 29 patients diagnosed with triple healing (histological healing associated with intact ileal and colonic permeability) at inclusion experienced relapse. Conclusions Morphological and functional evaluation using pCLE offers superior prognostic value and is emerging as a possible therapeutic target for the prevention of clinical and endoscopic relapses in UC.