Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11679
Title: Toll-like receptor 3 and 7/8 function is impaired in hepatitis C rapid fibrosis progression post-liver transplantation.
Austin Authors: Howell, Jessica;Sawhney, R;Skinner, N;Gow, Paul J ;Angus, Peter W ;Ratnam, D;Visvanathan, K
Affiliation: Liver Transplant Unit, Austin Hospital, Department of Medicine, University of Melbourne, Australia
Issue Date: 20-Feb-2013
Publication information: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2013; 13(4): 943-53
Abstract: Recurrence of hepatitis C (HCV) postliver transplant is universal, with a subgroup developing rapid hepatic fibrosis. Toll-like receptors (TLRs) are critical to innate antiviral responses and HCV alters TLR function to evade immune clearance. Whether TLRs play a role in rapid HCV recurrence posttransplant is unknown. We stimulated peripheral blood mononuclear cells (PBMCs) from 70 patients with HCV postliver transplant with TLR subclass-specific ligands and measured cytokine production, TLR expression and NK cell function. Rate of fibrosis progression was calculated using posttransplant liver biopsies graded by Metavir scoring (F0-4; R=fibrosis stage/year posttransplant; rapid fibrosis defined as >0.4 units/year). Thirty of 70 (43%) patients had rapid fibrosis progression. PBMCs from HCV rapid-fibrosers produced less IFNα with TLR7/8 stimulation (p=0.039), less IL-6 at baseline (p=0.027) and with TLR3 stimulation (p=0.008) and had lower TLR3-mediated monocyte IL-6 production (p=0.028) compared with HCV slow fibrosers. TLR7/8-mediated NKCD56 dim cell secretion of IFNγ was impaired in HCV rapid fibrosis (p=0.006) independently of IFNα secretion and TLR7/8 expression, while cytotoxicity remained preserved. Impaired TLR3 and TLR7/8-mediated cytokine responses may contribute to aggressive HCV recurrence postliver transplantation through impaired immune control of HCV and subsequent activation of fibrogenesis.
Gov't Doc #: 23425350
URI: http://ahro.austin.org.au/austinjspui/handle/1/11679
DOI: 10.1111/ajt.12165
URL: https://pubmed.ncbi.nlm.nih.gov/23425350
Type: Journal Article
Subjects: Adult
Cross-Sectional Studies
Cytokines.metabolism
Disease Progression
Female
Hepacivirus
Hepatitis C.metabolism.physiopathology
Humans
Interferon-alpha.metabolism
Interferon-gamma.metabolism
Interleukin-6.metabolism
Killer Cells, Natural.cytology
Leukocytes, Mononuclear.cytology
Ligands
Liver Cirrhosis.physiopathology.virology
Liver Failure.therapy
Liver Transplantation
Male
Middle Aged
Prospective Studies
Recurrence
Toll-Like Receptor 3.metabolism
Toll-Like Receptor 7.metabolism
Toll-Like Receptor 8.metabolism
Appears in Collections:Journal articles

Show full item record

Page view(s)

12
checked on Nov 27, 2022

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.