Allograft inflammation and fibrosis among maintenance pediatric liver transplant recipients – genetic predisposition and antibodies, connecting the missing links.

Allograft inflammation and fibrosis among maintenance pediatric liver transplant recipients – genetic predisposition and antibodies, connecting the missing links. Varma S1, Latinne D2, Komuta M3, Ambroise J4, Smets F1, Baldin P3,Reding R5 , Stephenne X1, and Sokal EM1 Universite Catholique de Louvain, Cliniques Universitaires St Luc, 1Service de Gastroenterologie et Hepatologie Pediatrique, 3Service de Anatomopathologie 4 Centre for Applied Molecular Technologies (CTMA), Institut de Recherche Experimentale et Clinique (IREC), 5 Paediatric Surgery and Transplantation Unit, Brussels, Belgium Aim: To determine impact of HLA allo-antibodies, non-HLA auto-antibodies and HLA-DRB1 genotype amongst stable, long term pediatric liver transplantation (LT) recipients; on allograft health. Background: Role of HLA allo-antibodies and non-HLA auto-antibodies in late allograft fibrosis and inflammation is unclear in pediatric LT, though inferior long-term outcomes with class II donor specific HLA antibodies (Class-II DSA) post LT are suggested. HLA DRB1*03 or 04 genotype predisposes to auto-immune hepatitis (AIH), prototype of antibody related hepatic inflammation. Patients: Stable LT recipients transplanted in 2006-2012 and with >2 protocol biopsies were included. Autoimmune hepatitis, hepatitis B or C infection as indication of LT; ABOi graft, biliary or vascular complications post LT, re-transplantation were exclusion criteria. Methods Data were collected at 1-month pre-LT and simultaneous to last protocol biopsy. HLA, ANA, SMA, LKM antibodies, HLA-DRB1 genotype of recipients and histological aspects of biopsy, were collected. Histological parameters including rejection, bile duct proliferation, lobular inflammation, and portal tract infiltration were assessed while fibrosis was evaluated using Metavir and liver allograft fibrosis scoring (LAFSc). Results 15 of 89 included children had class-II DSA post LT. Class-II DSA was associated with allograft fibrosis using Metavir and LAFSc–score (p <0.01), specifically portal fibrosis (p<0.01). Class-II DSA, non-HLA auto-antibodies were associated with portal inflammation (p <0.01) and showed additive effects. Recipient HLA-DRB1*03 or 04 genotype was associated with portal fibrosis (p <0.05) and showed additive effect with class-II DSA. Conclusion Class-II DSA, non-HLA auto-antibodies, HLA-DRB1 genotype of recipient are important factors for long term allograft health and have additive effect.