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BACKGROUND: Liver transplantation for the most critically ill remains controversial; however, it is currently the only curative treatment option. AIM: To assess immediate posttransplant outcomes and compare the short (1 year) and long-term (6 years) posttransplant survival among cirrhotic patients stratified by disease severity. METHODS: We included cirrhotic patients undergoing liver transplantation between 2015 and 2019 and categorized them into compensated cirrhosis (CC), decompensated cirrhosis (DC), and acute-on-chronic liver failure (ACLF). ACLF was further divided into severity grades. Our primary outcomes of interest were total days of intensive care unit (ICU) and hospital stay, development of complications and posttransplant survival at 1 and 6 years. RESULTS: 235 patients underwent liver transplantation (CC = 11, DC = 129 and ACLF = 95). Patients with ACLF had a significantly longer hospital stay [8.0 (6.0-13.0) vs CC, 6.0 (3.0-7.0), and DC 7.0 (4.5-10.0); P = 0.01] and developed more infection-related complications [47 (49.5%), vs CC, 1 (9.1%) and DC, 38 (29.5%); P < 0.01]. Posttransplant survival at 1- and 6-years was similar among groups (P = 0.60 and P = 0.90, respectively). ACLF patients stratified according to ACLF grade [ACLF-1 n = 40 (42.1%), ACLF-2 n = 33 (34.7%) and ACLF-3 n = 22 (23.2%)], had similar ICU and hospital stay length (P = 0.68, P = 0.54), as well as comparable frequencies of overall and infectious post-transplant complications (P = 0.58, P = 0.80). There was no survival difference between ACLF grades at 1 year and 6 years (P = 0.40 and P = 0.15). CONCLUSION: Patients may benefit from liver transplantation regardless of the cirrhosis stage. ACLF patients have a longer hospital stay and frequency of infectious complications; however, excellent, and comparable 1 and 6-year survival rates support their enlisting and transplantation including those with ACLF-3.
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Insuficiencia Hepática Crónica Agudizada , Trasplante de Hígado , Humanos , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/cirugía , Insuficiencia Hepática Crónica Agudizada/etiología , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Pronóstico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugíaRESUMEN
BACKGROUND & AIMS: Patients with advanced cirrhosis often have immune dysfunction and are more susceptible to infections. Galectin-3 is a ß-galactoside-binding lectin implicated in inflammation, immune regulation and liver fibrosis. We aim to investigate galectin-3 expression in advanced cirrhosis and its ability to predict post-transplant infectious complications. METHODS: We collected sera and liver samples from 129 cirrhotic patients at the time of liver transplantation and from an external cohort of 37 patients with alcoholic liver disease including alcoholic hepatitis (AH) at the time of diagnosis. Galectin-3 was assessed by ELISA, real-time PCR, immunohistochemistry and RNA-seq. Receiver operating characteristic curves and Cox proportional-hazards regression analysis were performed to assess the predictive power of galectin-3 for disease severity and post-transplant infections. RESULTS: Increased galectin-3 levels were found in advanced cirrhosis. Galectin-3 significantly correlated with disease severity parameters and inflammatory markers. Galectin-3 had significant discriminating power for compensated and advanced cirrhosis (AUC = 0.78/0.84, circulating/liver galectin-3; p < .01), and was even higher to discriminate severe AH (AUC = 0.95, p < .0001). Cox Proportional-hazard model showed that galectin-3, MELD-Na and the presence of SIRS predict the development of post-transplant infectious complications. Patients with circulating galectin-3 (>16.58 ng/ml) were at 2.19-fold 95% CI (1.12-4.29) increased risk, but when combined with MELD-Na > 20.0 and SIRS, the risk to develop post-transplant infectious complications, increased to 4.60, 95% CI (2.38-8.90). CONCLUSION: Galectin-3 is a novel biological marker of active inflammation and disease severity that could be clinically useful alone or in combination with other scores to discriminate advanced cirrhosis and predict post-transplant infectious complications.
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Hepatitis Alcohólica , Hepatopatías , Trasplante de Hígado , Biomarcadores , Proteínas Sanguíneas , Galectina 3 , Galectinas , Hepatitis Alcohólica/complicaciones , Humanos , Inflamación , Cirrosis Hepática/complicaciones , Hepatopatías/complicaciones , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria SistémicaRESUMEN
Independent predictors of mortality for COVID-19 patients have been identified upon hospital admission; however, how they behave after hospitalization remains unknown. The aim of this study is to identify clinical and laboratory parameters from admission to discharge or death that distinguish survivors and non-survivors of COVID-19, including those with independent ability to predict mortality. In a cohort of 266 adult patients, clinical and laboratory data were analyzed from admission and throughout hospital stay until discharge or death. Upon admission, non-survivors had significantly increased C reactive protein (CRP), neutrophil count, neutrophil to lymphocyte ratio (NLR) (p < 0.0001, each), ferritin (p < 0.001), and AST (aspartate transaminase) (p = 0.009) compared to survivors. During the hospital stay, deceased patients maintained elevated CRP (21.7 mg/dL [admission] vs. 19.3 [hospitalization], p = 0.060), ferritin, neutrophil count and NLR. Conversely, survivors showed significant reductions in CRP (15.8 mg/dL [admission] vs. 9.3 [hospitalization], p < 0.0001], ferritin, neutrophil count and NLR during hospital stay. Upon admission, elevated CRP, ferritin, and diabetes were independent predictors of mortality, as were persistently high CRP, neutrophilia, and the requirement of invasive mechanical ventilation during hospital stay. Inflammatory and clinical parameters distinguishing survivors from non-survivors upon admission changed significantly during hospital stay. These markers warrant close evaluation to monitor and predict patients' outcome once hospitalized.
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Severe COVID-19 is associated with a systemic hyperinflammatory response leading to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Galectin-3 is a ß-galactoside binding lectin known to drive neutrophil infiltration and the release of pro-inflammatory cytokines contributing to airway inflammation. Thus, we aimed to investigate the potential of galectin-3 as a biomarker of severe COVID-19 outcomes. We prospectively included 156 patients with RT-PCR confirmed COVID-19. A severe outcome was defined as the requirement of invasive mechanical ventilation (IMV) and/or in-hospital death. A non-severe outcome was defined as discharge without IMV requirement. We used receiver operating characteristic (ROC) and multivariable logistic regression analysis to determine the prognostic ability of serum galectin-3 for a severe outcome. Galectin-3 levels discriminated well between severe and non-severe outcomes and correlated with markers of COVID-19 severity, (CRP, NLR, D-dimer, and neutrophil count). Using a forward-stepwise logistic regression analysis we identified galectin-3 [odds ratio (OR) 3.68 (95% CI 1.47-9.20), p < 0.01] to be an independent predictor of severe outcome. Furthermore, galectin-3 in combination with CRP, albumin and CT pulmonary affection > 50%, had significantly improved ability to predict severe outcomes [AUC 0.85 (95% CI 0.79-0.91, p < 0.0001)]. Based on the evidence presented here, we recommend clinicians measure galectin-3 levels upon admission to facilitate allocation of appropriate resources in a timely manner to COVID-19 patients at highest risk of severe outcome.
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COVID-19/diagnóstico , COVID-19/virología , Galectinas/sangre , SARS-CoV-2 , Adulto , Anciano , Biomarcadores/sangre , Proteínas Sanguíneas , COVID-19/complicaciones , COVID-19/inmunología , Citocinas/metabolismo , Femenino , Humanos , Inflamación , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Infiltración Neutrófila , Gravedad del Paciente , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Síndrome de Dificultad Respiratoria/etiología , RiesgoRESUMEN
It has been recently reported that patients with cirrhosis have significantly higher mortality following severe acute respiratory syndrome coronavrisu 2 (SARS-CoV-2) infection compared with those without.1,2 Specifically, it was demonstrated that mortality was greater in those with advanced cirrhosis (Child-Pugh B and C), and that from cirrhotic patients experiencing SARS-CoV-2 infection, close to half suffer acute decompensation including acute-on-chronic liver failure (ACLF).2 Unfortunately, the presence of hepatic decompensation at baseline has been shown to be an independent predictor of all-cause mortality in patients with coronavirus disease 2019 (COVID-19).1 Patients with decompensated cirrhosis contracting COVID-19 have a poor outcome, with an overall reported mortality of over 30%.1.
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Insuficiencia Hepática Crónica Agudizada , COVID-19 , Citocinas , Humanos , Cirrosis Hepática , Pronóstico , SARS-CoV-2RESUMEN
INTRODUCTION AND OBJECTIVES: Acute on Chronic Liver Failure (ACLF) is characterized by organ failure and high 28-day mortality. Identifying clinical predictors associated with early mortality could have implications for the treatment of patients with ACLF. PATIENTS AND METHODS: Patients diagnosed with chronic liver failure that developed ACLF based on the EASL-CLIF Consortium definition admitted to the Intensive care unit of a tertiary hospital between 2012-2018 were included. Bivariate and multivariate Cox regression analyses were performed to identify factors associated with mortality. RESULTS: 148 patients (55% female) were diagnosed with ACLF of which 55% (nâ¯=â¯82) had ACLF grade 3, 28% (nâ¯=â¯41) grade 2 and 17% (nâ¯=â¯25) grade 1. The median age was 54 years (41-63). Hepatitis C virus (HCV) was the most frequent etiology in 29.8% (nâ¯=â¯44) of the patients with bacterial infection being the most predominant precipitant factor in 58.1% (nâ¯=â¯86). Ninety-day global cumulative survival was only 18%. When divided by grade, mortality reached to 10% in ACLF 3. Moreover, in the multivariate Cox regression analysis, renal failure (HR 3.26, 95% CI (2.13-4.99), brain failure (HR 1.37, 95% CI 1.09-2.04) and male sex (HR 1.62, 95% CI 1.10-2.40) were independent predictors of 28- and 90-day mortality. CONCLUSIONS: ACLF is a frequent syndrome among chronic liver disease patients. Brain and renal failure are significantly associated with higher mortality and are independent predictors of 28 and 90-day mortality.