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 ...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.展开更多
Background Severe alcohol-associated hepatitis(sAH)is a life-threatening condition with high mortality,where corticosteroid use is the only treatment that has shown short-term benefits.Pentoxifylline,an anti-tumour ne...Background Severe alcohol-associated hepatitis(sAH)is a life-threatening condition with high mortality,where corticosteroid use is the only treatment that has shown short-term benefits.Pentoxifylline,an anti-tumour necrosis factor-alpha agent,has been proposed for its potential to improve outcomes,especially in patients with acute kidney injury(AKI).We aimed to evaluate the impact of pentoxifylline on mortality in patients with sAH and AKI in a well-characterised global cohort.Methods We conducted a retrospective,registry-based study including patients meeting the National Institute on Alcohol Abuse and Alcoholism clinical criteria for sAH and AKI.Mortality was the primary endpoint,with liver transplantation as a competing risk.Statistical analysis included Cox regression and Kaplan-Meier survival estimates.Results We included 525 patients from 20 centres across eight countries.The median age was 48 years,with 26.1%females,and 76.9%had a history of cirrhosis.Multivariable Cox regression models showed that pentoxifylline use was not associated with survival(HR 1.20,95%CI 0.85 to 1.69,p=0.291).Factors associated with mortality included age(HR 1.23,95%CI 1.10 to 1.36,p<0.001),Model for End-Stage Liver Disease score at admission(HR 1.06,95%CI 1.04 to 1.08,p<0.001)and renal replacement therapy use(HR 1.39,95%CI 1.05 to 1.84,p=0.019).The main causes of death were multiple organ failure(42%),infections(10%),oesophageal varices bleeding(7%)and renal failure(6%).Conclusion Pentoxifylline showed no significant benefit on mortality in patients with sAH and AKI.Further studies are needed to refine treatment strategies for this high-risk group.展开更多
基金Supported by Health research fund"Fondo de Investigaciones Sanitarias"(to SV)Catalan Ministry of Health Stabilization ProgramInstitute of Health Carlos Ⅲ,Ministry of Science and Innovation,Grant No.PI09/00357,Madrid,Spain
文摘AIM: To analyze the cytokine production by peripheral blood cells from cirrhotic patients with and without TLR4 D299G and/or T399I polymorphisms.
基金Supported by(partially)from the Instituto de Salud CarlosⅢ,Madrid,Spain,No.PI0900357cofinanced by Fondos FEDER(Fondo Europeo de Desarrollo Regional)+3 种基金“Una manera de hacer Europa”,European Union,and CERCA Programme,Generalitat de CatalunyaSilvia Vidal was supported by Fondo de Investigaciones Sanitarias(FIS)a participant in the Program for Stabilization of Investigators of the Direcciód’Estrategia i Coordinaciódel Departament de Salut,Generalitat de CatalunyaEdilmar Alvarado-Tapias is a recipient of a“Río Hortega”fellowship grant from the Instituto de Salud CarlosⅢ,No.CM16/00133
文摘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.
基金support from the Chilean government through the Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT 1241450).
文摘Background Severe alcohol-associated hepatitis(sAH)is a life-threatening condition with high mortality,where corticosteroid use is the only treatment that has shown short-term benefits.Pentoxifylline,an anti-tumour necrosis factor-alpha agent,has been proposed for its potential to improve outcomes,especially in patients with acute kidney injury(AKI).We aimed to evaluate the impact of pentoxifylline on mortality in patients with sAH and AKI in a well-characterised global cohort.Methods We conducted a retrospective,registry-based study including patients meeting the National Institute on Alcohol Abuse and Alcoholism clinical criteria for sAH and AKI.Mortality was the primary endpoint,with liver transplantation as a competing risk.Statistical analysis included Cox regression and Kaplan-Meier survival estimates.Results We included 525 patients from 20 centres across eight countries.The median age was 48 years,with 26.1%females,and 76.9%had a history of cirrhosis.Multivariable Cox regression models showed that pentoxifylline use was not associated with survival(HR 1.20,95%CI 0.85 to 1.69,p=0.291).Factors associated with mortality included age(HR 1.23,95%CI 1.10 to 1.36,p<0.001),Model for End-Stage Liver Disease score at admission(HR 1.06,95%CI 1.04 to 1.08,p<0.001)and renal replacement therapy use(HR 1.39,95%CI 1.05 to 1.84,p=0.019).The main causes of death were multiple organ failure(42%),infections(10%),oesophageal varices bleeding(7%)and renal failure(6%).Conclusion Pentoxifylline showed no significant benefit on mortality in patients with sAH and AKI.Further studies are needed to refine treatment strategies for this high-risk group.
