Progressive Fibrosis Is Driven by Genetic Predisposition, Allo-immunity, and Inflammation in Pediatric Liver
S Varma1, J Ambroise2, M Komuta3
1Université Catholique de Louvain, Cliniques Universitaires St Luc, Department of Pediatrics, Service of pediatric gastroenterology and hepatology, Brussels, Belgium.
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.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:24Chronic Pancreatitis I: Introduction
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
01:24Tissue Transplantation
The Biology of Tissue Transplantation
The biology of tissue transplantation hinges on the Major Histocompatibility Complex (MHC) molecules. These molecules...
01:24Liver Regeneration
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
01:40Cell-mediated Immune Responses