Project description:Acute-on-chronic liver failure (ACLF) is a recently (re)defined syndrome of acute decompensation of cirrhosis that presents with extrahepatic organ failure(s) and poor outcome. Given the prominent role of inflammation and activation of coagulation in ACLF, we hypothesized that ACLF might be characterized by the generation of neutrophil extracellular traps (NETs), that could drive both activation of coagulation and progression of organ failure.MethodsWe measured markers of circulating DNA, activation of coagulation, inflammation, and oxidative stress in 52 patients with acute decompensation (AD) of cirrhosis and 57 patients with ACLF on admission, and compared levels with 40 healthy controls.ResultsAll analytes were higher in patients compared to controls. Plasma levels of cell-free DNA, but not of the specific NET marker myeloperoxidase-DNA complexes were higher in patients with ACLF compared to AD cirrhosis. In addition, TAT complexes (coagulation), IL-6 (inflammation), and TBARS (oxidative stress) were higher in ACLF compared to AD. Markers for activation of coagulation were not associated with circulating DNA, IL-6, or TBARS. In contrast, levels of circulating DNA, IL-6, and TBARS were higher in patients with more severe disease, higher in patients with organ failure, and higher in patients that died within 30 days of admission. Importantly, myeloperoxidase-DNA levels did not differ between patients with complications and poor outcome.ConclusionsCollectively, we show that cell-free DNA, inflammation, and oxidative stress are associated with outcomes in AD and ACLF, but not with activation of coagulation. Our data argue against a role of NETs in activation of coagulation and in progression of organ failure in patients with AD and ACLF.Lay summaryAcute-on-chronic liver failure is a devastating syndrome that can follow acute decompensation of chronic liver disease. Herein, we demonstrate that these patients accumulate DNA released from dying cells in their blood, and that the quantity of this DNA is related to the outcome of disease. We also show that outcome of disease is not related to recently described neutrophil extracellular traps, which have been shown in animal models to play vital roles in the progression of liver diseases.

Project description:BackgroundChemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value.MethodsBlood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels - Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC).Results21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. Plasma chemerin concentration were significantly higher in ICU patients than in HC at all time-points analyzed (p<0.0001). Moreover, they were higher in deceased patients compared to survivors (p<0.05). Logistic univariate regression and multivariate analysis demonstrated that chemerin level at day 14 of admission was an independent risk factor for death. Accordingly, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein and tumor necrosis factor α. Finally, IHC analysis revealed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts in advanced acute respiratory distress syndrome (ARDS).DiscussionIncreased plasma chemerin levels are a marker of severity and may predict death of COVID-19 patients. However, multicentric studies are needed, before chemerin can be considered as a biomarker of severity and death used in daily clinical practice. Further studies are also necessary to identify the precise mechanisms of the chemerin/ChemR23 system in ARDS secondary to viral pneumonia.

Project description:Background: Soluble CD163 (sCD163) is a scavenger receptor membrane protein expressed almost exclusively on Kupffer cells and other macrophages. It was found to be associated with the severity of liver cirrhosis. The aim of the present study was to determine whether the novel biomarker sCD163 predicts outcomes in patients with decompensated cirrhosis. Materials and Methods: A single-center, observational, prospective study with 345 decompensated cirrhosis patients was conducted in the Gastroenterology Department between January 2017 and December 2020. Their plasma samples were tested by enzyme-linked immunosorbent assay (ELISA) for sCD163 within 24 hours of admission. These patients were followed up at 28 days, 3 months and 6 months. The independent risk factors were identified with uni- and multivariate logistic regression analyses. We evaluated the predictive performance of the new scoring system (including sCD163) and the original scoring system. Results: The sCD163 level was significantly higher in non-surviving patients than in surviving patients. Positive associations were found between sCD163 levels and the Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD) and albumin-bilirubin (ALBI) scores. Logistic regression confirmed that sCD163 was an independent risk factor for 28-day, 3-month, and 6-month mortality. The areas under the receiver operating characteristic curves (AUROCs) of the use of sCD163 for the prediction of 28-day, 3-month, and 6-month mortality were relatively higher (AUROCs: 0.856; 0.823 and 0.811, respectively). The AUROCs of the new scores obtained by adding sCD163 to the original scoring systems (CTP + sCD163, MELD + sCD163 and ALBI + sCD163) showed that the new scoring systems had better predictive performance than the original scoring systems at all time points (P < 0.001). Conclusion: sCD163 is a prognostic predictor of short-term and long-term outcomes in decompensated cirrhosis patients. Accordingly, the addition of sCD163 to the original clinical scoring systems improved their prognostic performance.

Dataset Information

Low circulating chemerin levels correlate with hepatic dysfunction and increased mortality in decompensated liver cirrhosis.

Publications

Low circulating chemerin levels correlate with hepatic dysfunction and increased mortality in decompensated liver cirrhosis.

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