Baseline quantitative histology in therapeutics trials reveals villus atrophy in most patients with coeliac disease who appear well controlled on gluten‐free diet

Background The prevalence and severity of duodenal injury in coeliac disease patients controlled on a gluten-free diet is unclear. Aims To use quantitative histology to assess duodenal injury in treated coeliac disease. Methods Quantitative histology in pre-treatment duodenal biopsies collected in clinical trials assessing an investigational immunotherapy for coeliac disease was analysed. Morphometric readings were converted to Marsh classifications. Results Ninety-three patients had duodenal biopsies. For well-oriented sections of second part biopsies, six (6%) patients were classified as Marsh 0 or 1, 30 (33%) as Marsh 2 and 56 (60%) as Marsh 3a or 3b. In second part biopsies from 78 seronegative patients on gluten-free diet >2 years, 27 (35%) were Marsh 2 and 45 (58%) were Marsh 3a or 3b. Distal compared to proximal duodenal biopsies had significantly higher villus height to crypt depth ratios (median, third part: 2.1 vs bulb: 1.4; P < 0.0001) and higher intraepithelial lymphocyte density (44 vs 30; P = 0.0002). The sum of paired villus height and adjacent crypt depth measurements was correlated strongly with villus height (rs = 0.82, P < 10−10). At least one biopsy was graded Marsh 3a or worse in all 26 patients who had serial biopsies from the bulb, first, second and third part, but was overlooked in 20 patients by subjective histology. Conclusions Quantitative histology in well-oriented biopsy sections reveals villus atrophy in the majority of patients with coeliac disease who appear well controlled on gluten-free diet. Standardisation of biopsy collection, processing and evaluation could substantially improve the value of follow-up biopsies in coeliac disease.