microRNA associated with hepatocyte injury and systemic inflammation may predict adverse outcomes in cirrhotic patients.

Humans Liver Cirrhosis / genetics MicroRNAs / genetics Male Female Middle Aged Inflammation / genetics Prognosis Hepatocytes / metabolism Biomarkers / blood Adult Aged Acute-On-Chronic Liver Failure / genetics Case-Control Studies Liver Transplantation / adverse effects

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
11 Oct 2024
Historique:
received: 31 01 2023
accepted: 06 09 2024
medline: 12 10 2024
pubmed: 12 10 2024
entrez: 11 10 2024
Statut: epublish

Résumé

As the global prevalence of chronic liver disease continues to rise, the need to determine which patients will develop end-stage liver disease and require liver transplantation is increasingly important. However, current prognostic models perform sub-optimally. We aim to determine microRNA profiles associated with clinical decompensation and mortality/transplantation within 1 year. We examined microRNA expression profiles in plasma samples from patients across the spectrum of cirrhosis (n = 154), acute liver failure (ALF) (n = 22), sepsis (n = 20) and healthy controls (HC) (n = 20). We demonstrated that a microRNA-based model (miR-24 and -27a) associated with systemic inflammation differentiated decompensated cirrhosis states from compensated cirrhosis and HC (AUC 0.77 (95% CI 0.69-0.85)). 6 patients within the compensated cirrhosis group decompensated the subsequent year and their exclusion improved model performance (AUC 0.81 (95% CI 0.71-0.89)). miR-191 (associated with liver injury) predicted risk of mortality across the cohort when acutely decompensated and acute-on-chronic-liver failure patients were included. When they were excluded miR-24 (associated with systemic inflammation) predicted risk of mortality. Our findings demonstrate that microRNA associated with systemic inflammation and liver injury predict adverse outcomes in cirrhosis. miR-24 and -191 require further investigation as prognostic biomarkers and therapeutic targets for patients with liver disease.

Identifiants

DOI: 10.1038/s41598-024-72416-w PMID: 39394217
pubmed: 39394217
doi: 10.1038/s41598-024-72416-w
pii: 10.1038/s41598-024-72416-w
doi:

Substances chimiques

MicroRNAs 0
Biomarkers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

23831

Subventions

Organisme : Roche Organ Transplant Research Foundation
ID : 1-3336
Organisme : National Institute for Health and Care Research Guy's and St Thomas' Biomedical Research Centre
ID : RE12566

Informations de copyright

© 2024. The Author(s).

Références

Pimpin, L. et al. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. J. Hepatol. 69(3), 718–735 (2018).
pubmed: 29777749 doi: 10.1016/j.jhep.2018.05.011
Karlsen, T. H. et al. The EASL-Lancet Liver Commission: Protecting the next generation of Europeans against liver disease complications and premature mortality. Lancet 399(10319), 61–116 (2022).
pubmed: 34863359 doi: 10.1016/S0140-6736(21)01701-3
de Franchis, R., Bosch, J., Garcia-Tsao, G., Reiberger, T. & Ripoll, C. Baveno VII—Renewing consensus in portal hypertension. J. Hepatol. 76(4), 959–974 (2022).
pubmed: 35120736 doi: 10.1016/j.jhep.2021.12.022
Trebicka, J. et al. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology. J. Hepatol. 73(4), 842–854 (2020).
pubmed: 32673741 doi: 10.1016/j.jhep.2020.06.013
Åberg, F. et al. Development and validation of a model to predict incident chronic liver disease in the general population: The CLivD score. J. Hepatol. 77, 302–311 (2022).
pubmed: 35271949 doi: 10.1016/j.jhep.2022.02.021
Innes, H. et al. Performance of routine risk scores for predicting cirrhosis-related morbidity in the community. J. Hepatol. 77, 365–376 (2022).
pubmed: 35271950 doi: 10.1016/j.jhep.2022.02.022
Child, C. G. & Turcotte, J. G. Surgery and portal hypertension. Major Probl. Clin. Surg. 1, 1–85 (1964).
pubmed: 4950264
Pugh, R. N., Murray-Lyon, I. M., Dawson, J. L., Pietroni, M. C. & Williams, R. Transection of the oesophagus for bleeding oesophageal varices. Br. J. Surg. 60(8), 646–649 (1973).
pubmed: 4541913 doi: 10.1002/bjs.1800600817
Kamath, P. S. et al. A model to predict survival in patients with end-stage liver disease. Hepatology 33(2), 464–470 (2001).
pubmed: 11172350 doi: 10.1053/jhep.2001.22172
Jalan, R. et al. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J. Hepatol. 61(5), 1038–1047 (2014).
pubmed: 24950482 doi: 10.1016/j.jhep.2014.06.012
Jalan, R. et al. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J. Hepatol. 62(4), 831–840 (2015).
pubmed: 25463539 doi: 10.1016/j.jhep.2014.11.012
Cisilotto, J. et al. MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction. Sci. Rep. 10(1), 100 (2020).
pubmed: 31919459 pmcid: 6952390 doi: 10.1038/s41598-019-56630-5
Benz, F., Roy, S., Trautwein, C., Roderburg, C. & Luedde, T. Circulating MicroRNAs as biomarkers for sepsis. Int. J. Mol. Sci. 17(1), 78 (2016).
pubmed: 26761003 pmcid: 4730322 doi: 10.3390/ijms17010078
Cortez-Dias, N. et al. Circulating miR-122-5p/miR-133b ratio is a specific early prognostic biomarker in acute myocardial infarction. Circ. J. 80(10), 2183–2191 (2016).
pubmed: 27593229 doi: 10.1253/circj.CJ-16-0568
Elhendawy, M. et al. MicroRNA signature in hepatocellular carcinoma patients: identification of potential markers. Mol. Biol. Rep. 47, 4945–4953 (2020).
pubmed: 32430845 doi: 10.1007/s11033-020-05521-4
Blaya, D. et al. Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure. JHEP Rep. 3(2), 100233 (2021).
pubmed: 33665588 pmcid: 7902550 doi: 10.1016/j.jhepr.2021.100233
Tavabie, O. D. et al. A novel microRNA-based prognostic model outperforms standard prognostic models in patients with acetaminophen-induced acute liver failure. J. Hepatol. 75, 424–434 (2021).
pubmed: 33857547 pmcid: 10668489 doi: 10.1016/j.jhep.2021.03.013
Salehi, S. et al. Human liver regeneration is characterized by the coordinated expression of distinct microRNA governing cell cycle fate. Am. J. Transpl. 13(5), 1282–1295 (2013).
doi: 10.1111/ajt.12183
Salehi, S. et al. Serum MicroRNA signatures in recovery from acute and chronic liver injury and selection for liver transplantation. Liver Transpl. 26(6), 811–822 (2020).
pubmed: 32297687 doi: 10.1002/lt.25781
Takahara, T. et al. Dual expression of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers. Hepatology 26(6), 1521–1529 (1997).
pubmed: 9397993 doi: 10.1002/hep.510260620
Winkler, M. et al. Endothelial GATA4 controls liver fibrosis and regeneration by preventing a pathogenic switch in angiocrine signaling. J. Hepatol. 74(2), 380–393 (2021).
pubmed: 32916216 doi: 10.1016/j.jhep.2020.08.033
Bourbonnais, E. et al. Liver fibrosis protects mice from acute hepatocellular injury. Gastroenterology 142(1), 130–9.e4 (2012).
pubmed: 21945831 doi: 10.1053/j.gastro.2011.09.033
Najafzadeh, B. et al. The oncogenic potential of NANOG: An important cancer induction mediator. J. Cell Physiol. 236(4), 2443–2458 (2021).
pubmed: 32960465 doi: 10.1002/jcp.30063
Chen, T., Du, J. & Lu, G. Cell growth arrest and apoptosis induced by Oct4 or Nanog knockdown in mouse embryonic stem cells: A possible role of Trp53. Mol. Biol. Rep. 39(2), 1855–1861 (2012).
pubmed: 21706347 doi: 10.1007/s11033-011-0928-6
Jeter, C. R. et al. Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells 27(5), 993–1005 (2009).
pubmed: 19415763 doi: 10.1002/stem.29
Yu, K. Q. et al. Long non-coding RNA ANRIL regulates inflammatory factor expression in ulcerative colitis via the miR-191-5p/SATB1 axis. Inflammation 47(2), 513–529 (2024).
pubmed: 37985573 doi: 10.1007/s10753-023-01925-z
Shihana, F. et al. MicroRNAs signature panel identifies heavy drinkers with alcohol-associated cirrhosis from heavy drinkers without liver injury. Biology 12(10), 1314 (2023).
pubmed: 37887024 pmcid: 10604848 doi: 10.3390/biology12101314
Arroyo, V. et al. The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis. J. Hepatol. 74(3), 670–685 (2021).
pubmed: 33301825 doi: 10.1016/j.jhep.2020.11.048
Costa, D. et al. Systemic inflammation increases across distinct stages of advanced chronic liver disease and correlates with decompensation and mortality. J. Hepatol. 74(4), 819–828 (2021).
pubmed: 33075344 doi: 10.1016/j.jhep.2020.10.004
Naqvi, A. R., Fordham, J. B. & Nares, S. miR-24, miR-30b, and miR-142-3p regulate phagocytosis in myeloid inflammatory cells. J. Immunol. 194(4), 1916–1927 (2015).
pubmed: 25601927 doi: 10.4049/jimmunol.1401893
Saha, B., Momen-Heravi, F., Kodys, K. & Szabo, G. MicroRNA cargo of extracellular vesicles from alcohol-exposed monocytes signals Naive monocytes to differentiate into M2 macrophages. J. Biol. Chem. 291(1), 149–159 (2016).
pubmed: 26527689 doi: 10.1074/jbc.M115.694133
Gierlikowski, W. & Gierlikowska, B. MicroRNAs as regulators of phagocytosis. Cells 11(9), 1380 (2022).
pubmed: 35563685 pmcid: 9106007 doi: 10.3390/cells11091380
Villanueva, C. et al. Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis. J. Hepatol. 77, 1014–1025 (2022).
pubmed: 35661713 doi: 10.1016/j.jhep.2022.05.021
Patel, V. C. et al. Rifaximin-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial. J. Hepatol. 76(2), 332–342 (2022).
pubmed: 34571050 doi: 10.1016/j.jhep.2021.09.010
Villanueva, C. et al. β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 393(10181), 1597–1608 (2019).
pubmed: 30910320 doi: 10.1016/S0140-6736(18)31875-0
Salehi, S. et al. Rifaximin reduces the incidence of spontaneous bacterial peritonitis, variceal bleeding and all-cause admissions in patients on the liver transplant waiting list. Aliment Pharmacol. Ther. 50(4), 435–441 (2019).
pubmed: 31169941 pmcid: 6816014 doi: 10.1111/apt.15326
Tonon, M. et al. A new clinical and prognostic characterization of the patterns of decompensation of cirrhosis. J. Hepatol. 80(4), 603–609 (2024).
pubmed: 38110003 doi: 10.1016/j.jhep.2023.12.005
Moreau, R. et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 144(7), 1426–1437 (2013).
pubmed: 23474284 doi: 10.1053/j.gastro.2013.02.042
Xiang, X. et al. Interleukin-22 ameliorates acute-on-chronic liver failure by reprogramming impaired regeneration pathways in mice. J Hepatol 72(4), 736–745 (2020).
pubmed: 31786256 doi: 10.1016/j.jhep.2019.11.013
Barber, K. et al. Elective liver transplant list mortality: Development of a United Kingdom end-stage liver disease score. Transplantation 92(4), 469–476 (2011).
pubmed: 21775931 doi: 10.1097/TP.0b013e318225db4d
Piano, S., Bunchorntavakul, C., Marciano, S. & Reddy, K. R. Infections in cirrhosis. Lancet Gastroenterol. Hepatol. https://doi.org/10.1016/S2468-1253(24)00078-5 (2024).
doi: 10.1016/S2468-1253(24)00078-5 pubmed: 39243796
von Elm, E. et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies. Bmj 335(7624), 806–808 (2007).
doi: 10.1136/bmj.39335.541782.AD
Conn, H. O. et al. Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology 72(4 Pt 1), 573–583 (1977).
pubmed: 14049 doi: 10.1016/S0016-5085(77)80135-2
QIAGEN. Qiagen Kit Handbooks. 2020. Accessed online 22/07/2020: https://www.qiagen.com/gb/service-and-support/learning-hub/search-resources/#filters=%7BF321478C-FDDA-437F-BE0B-87001D9936D3%7D .
Blondal, T. et al. Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods 59(1), S1-6 (2013).
pubmed: 23036329 doi: 10.1016/j.ymeth.2012.09.015
GeneGo. MetaCore. 2020. Accessed 28 Jun 2020.
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate—A practical and powerful approach to multiple testing. J. R. Stat. Soc. 57, 289–300 (1995).
doi: 10.1111/j.2517-6161.1995.tb02031.x

Auteurs

Oliver D Tavabie (OD)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
Department of Inflammation Biology, School of Immunity and Microbial Sciences, King's College London, London, UK.

Vishal C Patel (VC)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
Department of Inflammation Biology, School of Immunity and Microbial Sciences, King's College London, London, UK.
The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.

Siamak Salehi (S)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.

Marilena Stamouli (M)

The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.

Francesca M Trovato (FM)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
Department of Inflammation Biology, School of Immunity and Microbial Sciences, King's College London, London, UK.

Maria-Emanuela Maxan (ME)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.

Dhaarica Jeyanesan (D)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.

Savannah Rivera (S)

The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.

Salma Mujib (S)

Department of Inflammation Biology, School of Immunity and Microbial Sciences, King's College London, London, UK.

Ane Zamalloa (A)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.

Eleanor Corcoran (E)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.

Krishna Menon (K)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.

Andreas Prachalias (A)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.

Michael A Heneghan (MA)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
Department of Inflammation Biology, School of Immunity and Microbial Sciences, King's College London, London, UK.

Kosh Agarwal (K)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.

Mark J W McPhail (MJW)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
Department of Inflammation Biology, School of Immunity and Microbial Sciences, King's College London, London, UK.

Varuna R Aluvihare (VR)

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK. varuna.aluvihare@kcl.ac.uk.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Cirrhose du foie › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Diagnostic › Pronostic › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Cellules › Cellules épithéliales › Hépatocytes › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Insuffisance hépatique › Défaillance hépatique › Défaillance hépatique aigüe › Insuffisance hépatique aigüe sur chronique › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › microRNA associated with hepatocyte injury and...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation de tissu › Transplantation hépatique › microRNA associated with hepatocyte injury and...