CD, or not CD, that is the question: a digital interobserver agreement study in coeliac disease

James Denholm, Benjamin A Schreiber, Florian Jaeckle, Mike N Wicks, Emyr W Benbow, Tim S Bracey, James Y H Chan, Lorant Farkas, Eve Fryer, Kishore Gopalakrishnan, Caroline A Hughes, Kathryn J Kirkwood, Gerald Langman, Betania Mahler-Araujo, Raymond F T McMahon, Khun La Win Myint, Sonali Natu, Andrew Robinson, Ashraf Sanduka, Katharine A SheppardYee Wah Tsang, Mark J Arends, Elizabeth J Soilleux

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis.

DESIGN: We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase 1, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase 2, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.

RESULTS: We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen's kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen's kappa coefficient of 0.67 (±0.09).

CONCLUSION: We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited interobserver agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the importance of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using artificial intelligence.

Original languageEnglish
JournalBMJ Open Gastroenterology
Issue number1
Publication statusPublished - 1 Feb 2024


  • Humans
  • Celiac Disease/diagnosis
  • Transglutaminases
  • Artificial Intelligence
  • Observer Variation
  • Immunoglobulin A


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