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Project description:BACKGROUND In the intensive care unit (ICU), critically ill patients with cirrhosis and acute-on-chronic liver failure (ACLF) continue to have high mortality rates. The AARC ACLF score is a simple, newly-developed score based on Asian ACLF patients, which performs well in prognosis. The present study attempted to verify the prognostic ability of AARC ACLF in non-Asian critically ill patients with cirrhosis and ACLF. MATERIAL AND METHODS We enrolled 786 patients. Relevant clinical data were collected within 24 h after admission to compare the differences between survivors and non-survivors, and all the patients were followed up for at least 180 days. RESULTS The 28-day, 90-day, and 180-day mortality rates were 28.9% (227/786), 36.4% (286/786), and 40.3% (317/786), respectively. Multivariate Cox regression analysis showed that AARC ACLF score (HR: 1.375, 95% CI: 1.247-1.516, P<0.001) was an independent predictive factor of 28-day mortality, and the AUROC of the predictive ability in 28-day mortality of the AARC ACLF score was 0.754. In addition, the AARC ACLF score was regraded into 3 classes (low risk: AARC ACLF <9, intermediate risk: 9≤ AARC ACLF <12, and high risk: AARC ACLF ≥12). The AARC ACLF score can be used for dynamic assessment by retest at days 4-7. CONCLUSIONS The AARC ACLF score has a good predictive value for 28-day, 90-day, and 180-day mortality in non-Asian critically ill patients with cirrhosis and ACLF, which is not inferior to CLIF-C ACLFsLact and other models. It is easy to use at bedside, and it is dynamic and reliable.
| S-EPMC7526342 | biostudies-literature
Project description:Neutrophils were isolated (using Ficoll, Dextran and water to lyse the red cells) from whole blood of 5 healthy subjects, 5 patients with stable cirrhosis and 5 patients with ACLF. RNA was then extracted and amplified 100 ng of RNA per sample were then hybridized on ClarionS array (Affymetrix, Thermofischer scientific)
2021-02-24 | GSE142254 | GEO
Project description: Not available
| S-EPMC11336529 | biostudies-literature
Project description:Gene expression profiling patients with cirrhosis and acute on chronic liver failure (ACLF)
| PRJNA596427 | ENA
Project description:Background & aimsMicroRNAs (miRNAs) circulate in several body fluids and can be useful biomarkers. The aim of this study was to identify blood-circulating miRNAs associated with cirrhosis progression and acute-on-chronic liver failure (ACLF).MethodsUsing high-throughput screening of 754 miRNAs, serum samples from 45 patients with compensated cirrhosis, decompensated cirrhosis, or ACLF were compared with those from healthy individuals (n = 15). miRNA levels were correlated with clinical parameters, organ failure, and disease progression and outcome. Dysregulated miRNAs were evaluated in portal and hepatic vein samples (n = 33), liver tissues (n = 17), and peripheral blood mononuclear cells (PBMCs) (n = 16).ResultsmiRNA screening analysis revealed that circulating miRNAs are dysregulated in cirrhosis progression, with 51 miRNAs being differentially expressed among all groups of patients. Unsupervised clustering and principal component analysis indicated that the main differences in miRNA expression occurred at decompensation, showing similar levels in patients with decompensated cirrhosis and those with ACLF. Of 43 selected miRNAs examined for differences among groups, 10 were differentially expressed according to disease progression. Moreover, 20 circulating miRNAs were correlated with model for end-stage liver disease and Child-Pugh scores. Notably, 11 dysregulated miRNAs were associated with kidney or liver failure, encephalopathy, bacterial infection, and poor outcomes. The most severely dysregulated miRNAs (i.e. miR-146a-5p, miR-26a-5p, and miR-191-5p) were further evaluated in portal and hepatic vein blood and liver tissue, but showed no differences. However, PBMCs from patients with cirrhosis showed significant downregulation of miR-26 and miR-146a, suggesting a extrahepatic origin of some circulating miRNAs.ConclusionsThis study is a repository of circulating miRNA data following cirrhosis progression and ACLF. Circulating miRNAs were profoundly dysregulated during the progression of chronic liver disease, were associated with failure of several organs and could have prognostic utility.Lay summaryCirculating miRNAs are small molecules in the blood that can be used to identify or predict a clinical condition. Our study aimed to identify miRNAs for use as biomarkers in patients with cirrhosis or acute-on-chronic liver failure. Several miRNAs were found to be dysregulated during the progression of disease, and some were also related to organ failure and disease-related outcomes.
| S-EPMC7902550 | biostudies-literature
Project description:Whole blood from 7 patients with stable cirrhosis, 7 patients with acutely decompensated cirrhosis without ACLF and 17 patients with ACLF (8 related to sepsis and 9 unrelated to sepsis) was sampled into tempus tubes (Applied biosystems, Ambion). The same method was used to sample whole blood from 7 healthy subjects and from 8 patients with septic shock without cirrhosis that were used as comparators.RNA was then extracted using the PerfectPure RNA blood kit (3 PRIME) according to manufactuter instructions. 100 ng of RNA per sample were then hybridized on Human Transcriptome Array 2.0
2021-02-24 | GSE142255 | GEO
Project description:Acute-on-chronic liver failure (ACLF) is a syndrome that develops in patients with acutely decompensated chronic liver disease. It is characterised by high 28-day mortality, the presence of one or more organ failures (OFs) and a variable but severe grade of systemic inflammation. Despite the peculiarity of each one, every definition proposed for ACLF recognizes it as a proper clinical entity. In this paper, we provide an overview of the diagnostic criteria proposed by the different scientific societies and the clinical characteristics of the syndrome. Established and experimental treatments are also described. Among the former, the most relevant are directed to support organ failures, treat precipitating factors and carry out early assessment for liver transplantation (LT). Further studies are needed to better clarify pathophysiology of the syndrome and discover new therapies.
| S-EPMC8509281 | biostudies-literature
Project description:Gene expression profiling of neutrophils from patients with cirrhosis and acute on chronic liver failure (ACLF)
| PRJNA596431 | ENA
Project description:BackgroundADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis that supports multiorgan function in patients with acute-on-chronic liver failure (ACLF). No data exist on whether ADVOS affects inflammatory cytokine levels, which play a relevant role in ACLF.AimOur aim was to quantify cytokine levels both before and after a single ADVOS treatment in patients with ACLF at a regular dialysis ward.Methods and resultsIn this prospective study, 15 patients (60% men) with ACLF and an indication for renal replacement therapy were included. Patient liver function was severely compromised, reflected by a median CLIF-consortium ACLF score of 38 (IQR 35; 40). Blood samples were directly taken before and after ADVOS dialysis. The concentration of cytokines for IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 were quantified via a cytometric bead array. We found no significant (p > 0.05) change in cytokine levels, even when patients were stratified for dialysis time (<480 min versus ≥480 min). The relevance of the assessed cytokines in contributing to systemic inflammation in ACLF was demonstrated by Ingenuity pathway analysis®.ConclusionConcentrations of pathomechanistically relevant cytokines remained unchanged both before and after ADVOS treatment in patients with ACLF.
| S-EPMC9144177 | biostudies-literature
Project description:Liver disease results in approximately 15,000 pediatric hospitalizations per year in the United States and is a significant burden to child health. Major etiologies of liver failure and indications for transplantation in children include: biliary atresia, metabolic/genetic conditions, toxins, infections, tumors, and immune-mediated liver/biliary injury. Children requiring transplantation are placed on the United Network of Organ Sharing waitlist including those with acute liver failure (ALF) and acute on chronic liver failure (ACLF). ALF is a clinical syndrome in which a previously healthy child develops rapid-onset hepatic dysfunction, and becomes critically ill with multiple organ dysfunction within days. ACLF, by contrast, is generally described as an acute decompensation of pre-existing chronic liver disease (CLD) brought on by a precipitating event, with higher risk of mortality. Children with ALF and ACLF receive multidisciplinary care in pediatric intensive care units (ICUs) due to multiple organ system involvement and high risk of decompensation in these patients. The care of these patients requires a holistic approach that addresses the complex interplay between hepatic and extra-hepatic organ systems. This review will define and describe ALF and ACLF in the pediatric population, and outline the effects of ALF and ACLF on individual organ systems with diagnostic and management considerations in the ICU while awaiting liver transplantation.
| S-EPMC8578785 | biostudies-literature