Expression of fibrosis-related genes in liver allografts : Association with histology and long-term outcome after pediatric liver transplantation

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Voutilainen , S H , Kosola , S K , Lohi , J , Jahnukainen , T , Pakarinen , M P & Jalanko , H J 2021 , ' Expression of fibrosis-related genes in liver allografts : Association with histology and long-term outcome after pediatric liver transplantation ' , Clinical Transplantation , vol. 35 , no. 8 , 14373 . https://doi.org/10.1111/ctr.14373

Title: Expression of fibrosis-related genes in liver allografts : Association with histology and long-term outcome after pediatric liver transplantation
Author: Voutilainen, Silja H.; Kosola, Silja K.; Lohi, Jouko; Jahnukainen, Timo; Pakarinen, Mikko P.; Jalanko, Hannu J
Contributor organization: Children's Hospital
HUS Children and Adolescents
Helsinki University Hospital Area
University of Helsinki
Lastenkirurgian yksikkö
Staff Services
HUSLAB
Department of Pathology
Date: 2021-08
Language: eng
Number of pages: 10
Belongs to series: Clinical Transplantation
ISSN: 0902-0063
DOI: https://doi.org/10.1111/ctr.14373
URI: http://hdl.handle.net/10138/340456
Abstract: Background Unexplained graft fibrosis and inflammation are common after pediatric liver transplantation (LT). Objective We investigated the graft expression of fibrogenic genes and correlated the findings with transplant histopathology and outcome. Methods Liver biopsies from 29 recipients were obtained at a median of 13.1 (IQR: 5.0-18.4) years after pediatric LT. Control samples were from six liver-healthy subjects. Hepatic expression of 40 fibrosis-related genes was correlated to histological findings: normal histology, fibrosis with no inflammation, and fibrosis with inflammation. Liver function was evaluated after a subsequent follow-up of 9.0 years (IQR: 8.0-9.4). Results Patients with fibrosis and no inflammation had significantly increased gene expression of profibrotic TGF-beta 3 (1.17 vs. 1.02 p = .005), CTGF (1.64 vs. 0.66 p = .014), PDGF-alpha (1.79 vs. 0.98 p = .049), PDGF -beta (0.99 vs. 0.76 p = .006), integrin-subunit-beta 1 (1.19 vs. 1.02 p = .045), alpha-SMA (1.12 vs. 0.58 p = .013), type I collagen (0.82 vs. 0.53 p = .005) and antifibrotic decorin (1.15 vs. 0.99 p = .045) compared to patients with normal histology. mRNA expression of VEGF A (0.84 vs. 1.06 p = .049) was lower. Only a few of the studied genes were upregulated in patients with both fibrosis and inflammation. The gene expression levels showed no association with later graft outcome. Conclusions Altered hepatic expression of fibrosis-related genes is associated with graft fibrosis without concurrent inflammation.
Subject: ACTIVATION
ANTIBODIES
GROWTH-FACTOR-BETA
HEPATIC STELLATE CELLS
INFLAMMATION
KEY
PATHWAYS
REJECTION
SYSTEMS
TISSUE
fibrosis
gene expression
inflammation
liver transplantation
pediatrics
3123 Gynaecology and paediatrics
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: acceptedVersion


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