Assessment of the Degree of Variation of Histologic Inflammation in Ulcerative Colitis

Introduction: Treatment of ulcerative colitis (UC) now includes mucosal healing. Adoption of histologic end points is hindered by a lack of evidence guiding optimal sampling, interpretation, and reproducibility of results. Methods: We analyzed biopsy fragments from colonoscopies in 92 patients with UC. Fragments were scored using 6-point histologic inflammatory activity (HIA) scale. Variability was determined using ordinal representations of HIA scores. The most frequently observed score and percentage of biopsy fragments with that score were determined for each biopsy, each segment, and across all 3 segments for each colonoscopy. Mean percentages and 95% confidence intervals (CIs) were calculated. Results: We reviewed 1802 biopsy fragments. The mean percentages of intrasegment biopsy fragments with the same HIA score were 85.5% (95% CI, 80.9% to 92.9%), 79.6% (95% CI, 76.0% to 87.3%), and 82.7% (95% CI, 79.1% to 90.0%) for the rectum, left colon, and right colon, respectively. The mean percentage of intersegment biopsy fragments with the same HIA score was 70.2% (95% CI, 65.7% to 82.5%). The mean percentages of intrabiopsy fragments with the same HIA score were 83.3% (95% CI, 77.6% to 93.5%), 83.6% (95% CI, 80.1% to 89.7%), and 90.2% (95% CI, 87.6% to 94.7%) for the rectum, left colon, and right colon, respectively. All 3 analyses revealed increased variation when a greater degree of histologic inflammation was present in the biopsies (mean HIA score ≥2). Conclusions: We found minimal variability between degree of inflammation among biopsy fragments within and among different colorectal segments in UC, suggesting that even a single biopsy would adequately reflect the inflammation of the entire colorectum. These findings have significant implications for the use of histology as a clinical target and trial end point in UC.