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Background: Histologic activity is recognized as an important predictor of relapse in ulcerative colitis (UC) patients. Current treatment targets aim at mucosal healing; however, many patients continue to have histologic activity. Goals: The aim was to assess histologic activity using the validated Nancy histologic index (NHI) score as a predictor of future relapse amongst UC patients in endoscopic and clinical remission. Study: In this retrospective cohort study, UC patients in clinical and endoscopic remission at a single tertiary center between 2015 and 2018, who underwent a surveillance colonoscopy were included. Clinical remission was defined by partial Mayo score (MSp) <2, and endoscopic remission was defined by Mayo endoscopic subscore (MES) ≤1. Histologic remission was defined by NHI <2. Predictive factors associated with the primary endpoint of clinical relapse were analyzed. Results: A total of 74 of 184 UC patients were included in the study. Amongst this cohort, 33 patients (45%) demonstrated histologic activity (NHI >1) at enrollment. The median follow-up time was 42 months (interquartile range: 26 to 63 mo) with median relapse free period of 30 months (interquartile range: 18 to 48 mo). Kaplan-Meier analysis demonstrated patients with MES 0 (P=0.02) and histologic remission (P<0.0001) had significantly longer relapse free survival. On multivariate analysis only histologic activity remained an independent risk factor of future clinical relapse (hazard ratio: 4.36, confidence interval: 1.68-11.27, P=0.002). Conclusion: Histologic remission using the NHI independently predicts significantly longer relapse free survival and may be a superior therapeutic target than endoscopic remission.

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