Morphological characterization of chronic antibody-mediated rejection in ABO-identical or ABO-compatible pediatric liver graft recipients

This study aims to define the morphological profile associated with the presence of donor-specific antibodies (DSAs) and/or C4d immunostaining in ABO-identical or compatible pediatric liver grafts. Ten-year protocol liver graft biopsies performed at 131.3 +/- 15.3 months after transplantation in 53 pediatric liver graft recipients were reviewed. Immunostaining for C4d was systematically performed and semiquantitatively analyzed. DSAs were concurrently quantified, and results were available for 44 patients. All biopsies demonstrated fibrotic changes with a mean liver allograft fibrosis score (LAFSc) of 5.1 +/- 2.2. A total of 31 (58%) biopsies exhibited C4d positivity. DSAs were detected in 20 (45%) patients, and mean maximal mean fluorescence intensity was 12,977 +/- 6731. LAFSc (6.3 +/- 1.3 versus 3.9 +/- 2.2; P = 0.008), perivenular fibrosis (2.7 +/- 0.5 versus 1.3 +/- 1.0; P < 0.001), and portal inflammation (1.4 +/- 0.8 versus 0.3 +/- 0.5; P = 0.009) were significantly higher in the double-DSA and C4d-positive group versus the double-negative group. We defined a histological scoring system from these results, which was integrated with the 2016 Banff definition and allowed reclassifying patients for the diagnosis of chronic active antibody-mediated rejection (cAMR; 11/53 versus 13/53). Diagnoses of probable cAMR according to Banff 2016 (n = 4) were unchanged, but 2 among the 9 patients classified as possible cAMR according to the 2016 Banff definition were excluded for this diagnostic when using our histological score. In conclusion, our results confirmed that perivenular fibrosis and portal inflammation in late pediatric liver graft biopsies are features of cAMR. Our histological score could improve the accuracy of the 2016 Banff definition for the diagnosis of cAMR. Liver Transplantation 24 897-907 2018 AASLD.