Abstract / Summary
Aims Histological assessment of duodenal biopsies remains central to the diagnosis of coeliac disease (CD), as detailed in the 2026 British Society for Gastroenterology guidelines on the diagnosis and management of CD, which recommend them as part of an integrated diagnostic approach. However, duodenal biopsies demonstrate a spectrum of mucosal changes, making interpretation inherently subjective. The reproducibility of histological diagnosis and classification has not been previously systematically evaluated. Methods A systematic review was registered with PROSPERO (CRD42021257108) and conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. MEDLINE, Embase and Cochrane Library Trials were searched from database inception to 13 February 2026. Data on study design and measures of interobserver agreement were extracted from full-text articles and synthesised. Results Twenty-three eligible studies evaluating interobserver agreement of histological diagnosis or classification of CD met the inclusion criteria. Considerable methodological heterogeneity limited direct comparison between studies and precluded meta-analysis. Interobserver agreement for the binary histological diagnosis of CD varied considerably between studies (κ=−0.07 to κ=1.00) and declined when observers graded specimens according to CD classification schemes. Factors affecting reproducibility included pathologist expertise, biopsy quality, endoscopic sampling strategy and number of categories in each grading scheme used. Conclusions Histological assessment remains central to the diagnosis of CD; however, its reproducibility is variable. Our results suggest that integrated diagnostic pathways that combine histological, serological and clinical information could maximise diagnostic accuracy.