PMID- 27333038
OWN - NLM
STAT- MEDLINE
DCOM- 20170223
LR  - 20181113
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 9
DP  - 2016 Jul
TI  - Progressive Fibrosis Is Driven by Genetic Predisposition, Allo-immunity, and 
      Inflammation in Pediatric Liver Transplant Recipients.
PG  - 346-355
LID - S2352-3964(16)30242-0 [pii]
LID - 10.1016/j.ebiom.2016.05.040 [doi]
AB  - AIM: To determine predisposing factors of idiopathic allograft fibrosis among 
      pediatric liver transplant recipients. BACKGROUND: Protocol biopsies (PB) from 
      stable liver transplant (LT) recipient children frequently exhibit idiopathic 
      fibrosis. The relation between allograft inflammation, humoral immune response 
      and fibrosis is uncertain. Also the role of HLA-DRB1 genotype has not been 
      evaluated, though it's associated with fibrosis in autoimmune hepatitis. PATIENTS 
      AND METHODS: This observational study, included 89 stable LT recipient 
      transplanted between 2004-2012 with mean follow-up of 4.3years, 281 serial PBs 
      (3.1 biopsy/child) and human leukocyte antigen (HLA) antibody data. PBs were 
      taken 1-2, 2-3, 3-5, 5-7, and 7-10years post-LT, and evaluated for inflammation 
      and fibrosis using liver allograft fibrosis score (LAFSc). The evolution of 
      fibrosis, inflammation and related predisposing factors were analysed. FINDINGS: 
      HLA-DRB1*03/04 allele and Class II DSA were significantly associated with portal 
      fibrosis (p=0.03; p=0.03, respectively). Portal inflammation was predisposed by 
      Class II DSA (p=0.02) and non-HLA antibody presence (p=0.01). Non-portal fibrosis 
      wasn't predisposed by inflammation. Lobular inflammation was associated with 
      non-HLA antibodies. INTERPRETATION: We conclusively demonstrated that allograft 
      inflammation results in fibrosis and is associated with post-LT Class II DSA and 
      non-HLA antibodies. The HLA-DRB1*03/04 allele caused genetic predisposition for 
      fibrosis. FUNDING: None.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Varma, S
AU  - Varma S
AD  - Universite Catholique de Louvain, Cliniques Universitaires St Luc, Department of 
      Pediatrics, Service of pediatric gastroenterology and hepatology, Brussels, 
      Belgium. Electronic address: sharat.varma@uclouvain.be.
FAU - Ambroise, J
AU  - Ambroise J
AD  - Universite Catholique de Louvain, Cliniques Universitaires St Luc, Centre for 
      applied molecular technologies (CTMA), Institute of experimental and clinical 
      research (IREC), Brussels, Belgium. Electronic address: 
      jerome.ambroise@uclouvain.be.
FAU - Komuta, M
AU  - Komuta M
AD  - Universite Catholique de Louvain, Cliniques Universitaires St Luc, Service of 
      anatomical pathology, Brussels, Belgium. Electronic address: 
      mina.komuta@uclouvain.be.
FAU - Latinne, D
AU  - Latinne D
AD  - Universite Catholique de Louvain, Cliniques Universitaires St Luc, Department of 
      clinical biology, Brussels, Belgium. Electronic address: 
      dominique.latinne@uclouvain.be.
FAU - Baldin, P
AU  - Baldin P
AD  - Universite Catholique de Louvain, Cliniques Universitaires St Luc, Service of 
      anatomical pathology, Brussels, Belgium. Electronic address: 
      pamela.baldin@uclouvain.be.
FAU - Reding, R
AU  - Reding R
AD  - Universite Catholique de Louvain, Cliniques Universitaires St Luc, Service of 
      pediatric surgery and transplantation, Brussels, Belgium. Electronic address: 
      raymond.reding@uclouvain.be.
FAU - Smets, F
AU  - Smets F
AD  - Universite Catholique de Louvain, Cliniques Universitaires St Luc, Department of 
      Pediatrics, Service of pediatric gastroenterology and hepatology, Brussels, 
      Belgium. Electronic address: francoise.smets@uclouvain.be.
FAU - Stephenne, X
AU  - Stephenne X
AD  - Universite Catholique de Louvain, Cliniques Universitaires St Luc, Department of 
      Pediatrics, Service of pediatric gastroenterology and hepatology, Brussels, 
      Belgium. Electronic address: xavier.stephenne@uclouvain.be.
FAU - Sokal, E M
AU  - Sokal EM
AD  - Universite Catholique de Louvain, Cliniques Universitaires St Luc, Department of 
      Pediatrics, Service of pediatric gastroenterology and hepatology, Brussels, 
      Belgium. Electronic address: etienne.sokal@uclouvain.be.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20160601
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Age Factors
MH  - Alleles
MH  - Biopsy
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Fibrosis
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA Antigens/immunology
MH  - HLA-DRB1 Chains/genetics
MH  - Humans
MH  - Immune System/metabolism
MH  - Inflammation/*pathology
MH  - Liver/metabolism/*pathology
MH  - Liver Diseases/genetics/pathology/therapy
MH  - *Liver Transplantation
MH  - Logistic Models
MH  - Male
MH  - Multivariate Analysis
MH  - Odds Ratio
MH  - Sex Factors
MH  - Transplantation, Homologous
PMC - PMC4972529
OTO - NOTNLM
OT  - *Donor-specific antibodies
OT  - *Fibrosis
OT  - *HLA antibodies
OT  - *HLA-DRB1
OT  - *Humoral immunity
OT  - *Pediatric liver transplantation
OT  - *Portal inflammation
EDAT- 2016/06/23 06:00
MHDA- 2017/02/24 06:00
PMCR- 2016/06/01
CRDT- 2016/06/23 06:00
PHST- 2016/04/11 00:00 [received]
PHST- 2016/05/22 00:00 [revised]
PHST- 2016/05/30 00:00 [accepted]
PHST- 2016/06/23 06:00 [entrez]
PHST- 2016/06/23 06:00 [pubmed]
PHST- 2017/02/24 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - S2352-3964(16)30242-0 [pii]
AID - 10.1016/j.ebiom.2016.05.040 [doi]
PST - ppublish
SO  - EBioMedicine. 2016 Jul;9:346-355. doi: 10.1016/j.ebiom.2016.05.040. Epub 2016 Jun 
      1.