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 ( TLR s), 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: TLR 1 (Asp248Ser and Ser602Ile), TLR 2 (Arg753Gln), TLR 3 (Leu412Phe), TLR 4 (Asp299Gly), TLR 5 (Arg392Stop), TLR 6 (Ser249Pro), TLR 7 (Gln11Leu), TLR 8 (Met1Val), and TLR 9 (−1237T/C and −1486C/T). The CC genotype of TLR 3 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 TLR 3 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 TLR 3 Leu412Phe CC genotype is independently associated with severity of hepatitis C recurrence after LT .