Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure
| العنوان: | Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure |
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| المؤلفون: | Mariuca Vasa-Nicotera, Elsa Solà, Juan José Lozano, Pau Sancho-Bru, Sara Fernández, Jonel Trebicka, Elisa Pose, Pere Ginès, Pedro Castro, Delia Blaya, Julia Sidorova, Robert Schierwagen, Joan Caballería, Mar Coll, Christian Jansen, Isabel Graupera |
| المصدر: | JHEP Reports JHEP Reports, Vol 3, Iss 2, Pp 100233-(2021) Blaya, D, Pose, E, Coll, M, Lozano, J J, Graupera, I, Schierwagen, R, Jansen, C, Castro, P, Fernandez, S, Sidorova, J, Vasa-Nicotera, M, Solà, E, Caballería, J, Trebicka, J, Ginès, P & Sancho-Bru, P 2021, ' Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure ', JHEP Reports, vol. 3, no. 2, 100233 . https://doi.org/10.1016/j.jhepr.2021.100233Test |
| مصطلحات موضوعية: | medicine.medical_specialty, Cirrhosis, NASH, non-alcoholic steatohepatitis, Encephalopathy, AST, aspartate aminotransferase, Disease, FoxO, forkhead box O, Chronic liver disease, Gastroenterology, Non-coding RNAs, CXCL10, C-X-C motif chemokine ligand 10, MELD, model for end-stage liver disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Model for End-Stage Liver Disease, ALT, alanine aminotransferase, TIPS, transjugular intrahepatic portosystemic shunt, Internal medicine, Internal Medicine, medicine, Immunology and Allergy, Decompensation, lcsh:RC799-869, EF CLIF, European Foundation for the Study of Chronic Liver Failure, INR, International Normalised Ratio, TGF, transforming growth factor, 030304 developmental biology, PBMCs, peripheral blood mononuclear cells, PCA, principal component analysis, 0303 health sciences, LDH, lactate dehydrogenase, Hepatology, business.industry, medicine.disease, 3. Good health, Circulating MicroRNA, ACLF, acute-on-chronic liver failure, 030220 oncology & carcinogenesis, lcsh:Diseases of the digestive system. Gastroenterology, qPCR, quantitative PCR, business, Liver decompensation, Biomarkers, MAPK, mitogen-activated protein kinase, Research Article |
| الوصف: | Background & Aims MicroRNAs (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). Methods Using 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). Results miRNA 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. Conclusions This 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 summary Circulating 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. Graphical abstract Highlights • Circulating miRNAs are dysregulated with cirrhosis progression and in patients with ACLF. • Patient decompensation is associated with important changes in the levels of circulating miRNAs. • A total of 11 circulating miRNAs were identified as associated with organ failure and 7 with poor outcome. • The miRNAs most dysregulated during cirrhosis progression were miR-146a, miR-26a, and miR-191. • miR-146a was dysregulated in PBMCs of patients with decompensated cirrhosis vs. compensated cirrhosis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2589-5559 |
| DOI: | 10.1016/j.jhepr.2021.100233 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::87d4e48212cb48cff68c240ced3c4227Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....87d4e48212cb48cff68c240ced3c4227 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 25895559 |
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| DOI: | 10.1016/j.jhepr.2021.100233 |