Galectin-3 is overexpressed in advanced cirrhosis and predicts post-liver transplant infectious complications.

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.

Renal and brain failure predict mortality of patients with acute-on-chronic liver failure admitted to the intensive care unit.

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% (n = 82) had ACLF grade 3, 28% (n = 41) grade 2 and 17% (n = 25) grade 1. The median age was 54 years (41-63). Hepatitis C virus (HCV) was the most frequent etiology in 29.8% (n = 44) of the patients with bacterial infection being the most predominant precipitant factor in 58.1% (n = 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.