Rapidity of fibrosis progression in liver transplant recipients with recurrent hepatitis C is influenced by toll-like receptor 3 polymorphism.
Liver transplantation activates the innate immune system through toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the association of single-nucleotide polymorphisms in TLR genes with the severity of hepatitis C virus recurrence after liver transplantation (LT). This is a two-center study of 176 adult patients who received a first LT from deceased donors for hepatitis C virus (HCV) cirrhosis. Eleven polymorphisms were evaluated by real-time polymerase chain reaction and melting curves analyses: TLR1 (Asp248Ser and Ser602Ile), TLR2 (Arg753Gln), TLR3 (Leu412Phe), TLR4 (Asp299Gly), TLR5 (Arg392Stop), TLR6 (Ser249Pro), TLR7 (Gln11Leu), TLR8 (Met1Val), and TLR9 (-1237T/C and -1486C/T). The CC genotype of TLR3 Leu412Phe in liver recipients was associated with severe recurrence (odds ratio (OR) = 2.01, 95% confidence interval (95% CI) = 1.02-3.93, p = 0.04). We also analyzed this polymorphism in 72 of their donors but no association was found with severity of HCV recurrence (p = 0.89). Multivariate analysis showed donor age older than 40 yr (OR=2.93; 95% CI = 1.49-5.8, p = 0.002) and the TLR3 Leu412Phe CC genotype (OR=2.02, 95%CI=1.01-4.05, p = 0.046) were independently associated with severe HCV recurrence. Our results show that the TLR3 Leu412Phe CC genotype is independently associated with severity of hepatitis C recurrence after LT.
Servicio de Medicina Interna, Instituto de Investigación Sanitaria Puerta de Hierro-Majadahonda (IDIPHIM), Madrid, Spain.
Maria J
MJ
Citores
Unidad de Trasplante Hepático, Hospital Clinic, IDIBAPS, CIBERedh, Barcelona, Spain.
Sofia
S
Pérez-Pulgar
Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
Ana
A
Duca
Unidad de Trasplante Hepático, Hospital Clinic, IDIBAPS, CIBERedh, Barcelona, Spain.
Gonzalo
G
Crespo
Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
Sara
S
de la Fuente
Grupo de Inmunogenética e Histocompatibilidad, Servicio de Inmunología, Instituto de Investigación Sanitaria Puerta de Hierro-Majadahonda, Madrid, Spain.
Carlos
C
Vilches
Unidad de Trasplante Hepático, Hospital Clinic, IDIBAPS, CIBERedh, Barcelona, Spain.
Miquel
M
Navasa
Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.|Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Valentin
V
Cuervas-Mons
D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012008:Recurrence; D012189:Retrospective Studies; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000378:metabolism; D066027:Transplant Recipients
D051196:Toll-Like Receptor 3; D004247:DNA
innate immunity; liver fibrosis; liver transplantation; recurrent hepatitis C; toll-like receptor 3