Introduction: Outcome after intestinal transplantation (ITx) has improved, however acute cellular rejection (ACR) remains a frequent challenge restricting long-term results. The gold standard for diagnosis of ACR is histological analysis of graft biopsies.

The diagnostic criteria for ACR were defined during the 2003 VIIIth International Small Bowel Transplant Symposium. Although this report provided consensus for international reporting, it has not been validated in a clinical setting. The aim of our study was to evaluate the reproducibility and the interobserver variability of the current histological scoring system in a multicenter study.

Methods: We retrospectively analyzed biopsies on newly stained slides from ITx patients from 3 hospitals. These slides were graded by 2 independent pathologists blinded to clinical information or original diagnosis. One reader was an experienced pathologist from an intestinal transplant center, the second reader was a last year pathology trainee. Biopsies were graded as: no signs of rejection, indeterminate for rejection (IFR) or ACR grade I to III based on current criteria. Only biopsies that were obtained endoscopically with at least 10 identifiable crypts were included in the final analysis.

Diagnoses were subsequently compared between the two readers (weighted Kappa Method) and to the original diagnosis made by several pathologists at other centers (intra-class correlation coefficient).

Results: 401 biopsies were evaluated from 45 patients (27 children, 18 adults) undergoing intestinal transplantation from 2000 to 2014. Median follow-up was 4.3 years (0–12,5). In total, 320 biopsies met inclusion criteria. 38 biopsies in 20 patients were originally described as showing ACR grade 1 to 3. Nine biopsies were IFR.

The overall weighted kappa value for the interobserver agreement was 0.82 (95% CI [0.752;0.882], p<0.001). The intraclass correlation coefficient comparing the pathology panel to the original diagnosis was 0.434 (95% CI [0.365;0.502]).

Conclusion: Despite the difference in clinical experience between the readers, there was a high level of interobserver agreement using the current histological criteria for acute cellular rejection. The lower degree of agreement with the original diagnosis may suggest a learning curve effect, or reflect the focal characteristic of ACR, differentially expressed in the newly cut slides. More importantly, part of the biopsies were evaluated with the old diagnostic criteria.