©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites
Germán Soriano, Carlos Guarner, Cándido Juárez, Juan Camilo Nieto, Oana Pavel, Cristina Gely, Maria Poca, Mar Concepción, Eva Román, Silvia Vidal, Elisabet Sánchez, Elida Oblitas, Carlos Guarner-Argente, Edilmar Alvarado-Tapias
Edilmar Alvarado-Tapias, Carlos Guarner-Argente, Elida Oblitas, Elisabet Sánchez, Eva Román, Mar Concepción, Maria Poca, Cristina Gely, Oana Pavel, Carlos Guarner, Germán Soriano, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona 08025, Spain
Edilmar Alvarado-Tapias, Elisabet Sánchez, Silvia Vidal, Cristina Gely, Juan Camilo Nieto, Carlos Guarner, Germán Soriano, Instituto de Salud Carlos III, Institut de Recerca IIB-Sant Pau, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès) 08193, Spain
Edilmar Alvarado-Tapias, Elisabet Sánchez, Eva Román, Maria Poca, Carlos Guarner, Germán Soriano, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid 28029, Spain
Silvia Vidal, Juan Camilo Nieto, Cándido Juárez, Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona 08025, Spain
Eva Román, Escola Universitària d’Infermeria EUI-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona 08025, Spain
Author contributions: Alvarado-Tapias E, Guarner-Argente C and Soriano G contributed to study concept and design; Alvarado-Tapias E, Poca M, Concepción M, Román E, Pavel O, Guarner-Argente C, Oblitas E, Sánchez E, Vidal S, Nieto JC and Juarez C contributed to acquisition of data; Alvarado-Tapias E, Soriano G and Vidal S contributed to analysis and interpretation of data; Alvarado-Tapias E and Soriano G contributed to drafting of the manuscript; Soriano G, Vidal S, Guarner C and Juarez C contributed to critical revision of the manuscript for important intellectual content; Alvarado-Tapias E, Soriano G and Vidal S contributed to statistical analysis; Soriano G contributed to study supervision.
Supported by (partially) from the Instituto de Salud Carlos III, Madrid, Spain, No. PI0900357; and cofinanced by Fondos FEDER (Fondo Europeo de Desarrollo Regional), “Una manera de hacer Europa”, European Union, and CERCA Programme, Generalitat de Catalunya; Silvia Vidal was supported by Fondo de Investigaciones Sanitarias (FIS) and is a participant in the Program for Stabilization of Investigators of the Direcció d’Estrategia i Coordinació del Departament de Salut, Generalitat de Catalunya; Edilmar Alvarado-Tapias is a recipient of a “Río Hortega” fellowship grant from the Instituto de Salud Carlos III, No. CM16/00133.
Institutional review board statement: This study was approved by the Ethics Committee of Hospital de la Santa Creu i Sant Pau. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki.
Informed consent statement: All study participants provided written informed consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
Correspondence to: Edilmar Alvarado-Tapias, MD, Research Fellow, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Mas Casanovas 90, Barcelona 08025, Spain.
ealvaradot@santpau.cat
Telephone: +34-93-5565920 Fax: +34-93-5565608
Received: November 16, 2017
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
Processing time: 70 Days and 22 Hours
AIM
To assess the relationship between the presence of toll-like receptor 4 (TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
