Toll-like receptor 3 and 7/8 function is impaired in hepatitis C rapid fibrosis progression post-liver transplantation.

摘要: 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 evade immune clearance. Whether TLRs play role in recurrence posttransplant unknown. We stimulated peripheral blood mononuclear cells (PBMCs) from 70 patients subclass-specific ligands measured cytokine production, expression NK cell function. Rate fibrosis progression was calculated using liver biopsies graded by Metavir scoring (F0–4; R = stage/year posttransplant; defined as >0.4 units/year). Thirty (43%) had progression. PBMCs rapid-fibrosers produced less IFNα TLR7/8 stimulation (p = 0.039), IL-6 at baseline 0.027) TLR3 0.008) lower TLR3-mediated monocyte production 0.028) compared slow fibrosers. TLR7/8-mediated NKCD56 dim secretion IFNγ impaired 0.006) independently expression, while cytotoxicity remained preserved. Impaired may contribute aggressive transplantation through control subsequent activation fibrogenesis.