Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.124
Peer-review started: November 17, 2017
First decision: December 1, 2017
Revised: December 16, 2017
Accepted: December 29, 2017
Article in press: December 29, 2017
Published online: January 27, 2018
To assess the relationship between the presence of toll-like receptor 4 (TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites.
We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus (HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma (beyond Milan’s criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299G and/or T399I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed.
We included 258 patients: 28 (10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms (polymorphism group) and 230 patients were not (wild-type group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group (P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli (51% vs 44%, P = 0.68), infections caused by gram-positive cocci (49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis (29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The one-year probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group (P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up.
Genetic polymorphisms D299G and/or T399I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections.
Core tip: Patients with cirrhosis present a high incidence of bacterial infections. Toll-like receptor (TLR) 4 genetic polymorphisms, particularly D299G, have been previously associated with an increased predisposition to infection in several populations. In the present study, genetic polymorphisms D299G and/or T399I of TLR4 do not seem to play a relevant role in the predisposition to develop bacterial infections or in the prognosis of cirrhotic patients with ascites. Age, serum creatinine, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy and the presence of hepatocellular carcinoma were independent predictive factors of mortality during follow-up.