Toll-like receptor 4 polymorphisms and the risk of gram-negative bacterial infections after liver transplantation

Background. Toll-like receptor 4 (TLR4) is the main immune molecule that recognizes lipopolysaccharide from gram-negative bacteria. Single-nucleotide polymorphisms (SNPs) in the TLR4 gene that impair lipopolysaccharide recognition may influence gram-negative bacterial infections after liver transplantation. Methods. TLR4 D299G and T399I SNPs were assessed in a cohort of 706 liver transplant recipients and were associated with the clinical characteristics and outcome of gram-negative bacterial infections. Cox proportional hazard model was performed to determine covariates associated with outcomes after gram-negative bacterial infections. Results. Of 706 patients, there were 108 with microbiologically confirmed gram-negative bacterial infections, 135 with clinically suspected but not confirmed infections, and 463 patients without gram-negative bacterial infections. The proportions of TLR4 D299G (5/108 [4.6%] vs. 32/463 [6.9%]; P=0.39) and T399I SNPs (19/108 [17.6%] vs. 68/463 [14.7%]; P=0.45) did not differ between those with or without microbiologically confirmed gram-negative bacterial infections. Female gender (odds ratio 2.30, 95% confidence interval [CI]1.50-3.53; P<0.001) and ulcerative colitis (odds ratio 2.18, 95% CI 1.08-4.38; P=0.03) were associated with gram-negative bacterial infections. Among 108 patients with gram-negative bacterial infections, alcoholic liver disease (relative risk [RR] 4.87, 95% CI 1.54-15.44; P=0.007), initial septic shock (RR 10.19, 95% CI 2.70-38.37; P=0.001), and nosocomially-acquired infection (RR 4.61, 95% CI 1.51-14.14; P=0.007) were significantly associated with 90-day mortality after gram-negative bacterial infections. In contrast, TLR4 D299G and T399I SNPs were not significantly associated with mortality after gram-negative bacterial infections. CONCLUSION.: In this cohort of liver transplant recipients with long-term follow-up, no significant association was observed between TLR4 D299G and T399I SNPs and the risk and outcome of gram-negative bacterial infections.