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Toll-like receptor 3 and 7/8 function is impaired in hepatitis C rapid fibrosis progression post-liver transplantation.
Howell, J; Sawhney, R; Skinner, N; Gow, P; Angus, P; Ratnam, D; Visvanathan, K.
Afiliación
  • Howell J; Liver Transplant Unit, Austin Hospital, Melbourne, Australia.
  • Sawhney R; Department of Medicine, University of Melbourne, Australia.
  • Skinner N; Liver Transplant Unit, Austin Hospital, Melbourne, Australia.
  • Gow P; Department of Medicine, University of Melbourne, Australia.
  • Angus P; Innate Immune Laboratory, Monash University, Melbourne, Australia.
  • Ratnam D; Liver Transplant Unit, Austin Hospital, Melbourne, Australia.
  • Visvanathan K; Department of Medicine, University of Melbourne, Australia.
Am J Transplant ; 13(4): 943-953, 2013 Apr.
Article en En | MEDLINE | ID: mdl-23425350
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Hígado / Hepatitis C / Receptor Toll-Like 3 / Receptor Toll-Like 7 / Receptor Toll-Like 8 Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2013 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Hígado / Hepatitis C / Receptor Toll-Like 3 / Receptor Toll-Like 7 / Receptor Toll-Like 8 Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2013 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos