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Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites

World Journal of Hepatology 2018年第1期10卷 124-133页

作者： Edilmar Alvarado-Tapias Carlos Guarner-Argente Elida Oblitas Elisabet Sánchez Silvia Vidal Eva Román Mar Concepción Maria Poca cristina gely Oana Pavel Juan Camilo Nieto Cándido Juárez Carlos Guarner Germán Soriano Department of Gastroenterology Hospital de la Santa Creu i Sant PauBarcelona 08025Spain Instituto de Salud Carlos III Institut de Recerca IIBSant PauUniversitat Autònoma de BarcelonaBellaterra(Cerdanyola del Vallès)08193Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Department of Immunology Hospital de la Santa Creu i Sant PauBarcelona 08025Spain Escola Universitària d’Infermeria EUI-Sant Pau Hospital de la Santa Creu i Sant PauBarcelona 08025Spain

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 D299 G and/or T399 I 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(wildtype 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 oneyear 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 D299 G and/or T399 I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections.

关键词： Cirrhosis Genetic polymorphisms Toll-like receptor 4 Bacterial infections Ascites

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