A PDGFRβ-based score predicts significant liver fibrosis in patients with chronic alcohol abuse, NAFLD and viral liver disease.
Adult
Algorithms
Animals
Biomarkers
Biopsy
Chemical and Drug Induced Liver Injury
/ complications
Disease Models, Animal
Endothelial Cells
/ metabolism
Extracellular Vesicles
/ metabolism
Fatty Liver, Alcoholic
/ complications
Female
Hepatic Stellate Cells
/ metabolism
Hepatitis, Viral, Animal
/ complications
Humans
Liver Cirrhosis
/ diagnosis
Male
Mice
Middle Aged
Non-alcoholic Fatty Liver Disease
/ complications
ROC Curve
Receptor, Platelet-Derived Growth Factor beta
/ genetics
Reproducibility of Results
Sensitivity and Specificity
Biomarker
Diagnosis
Extracellular vesicle
Hepatic stellate cell
Platelet derived growth factor receptor
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
28
02
2019
revised:
18
04
2019
accepted:
18
04
2019
pubmed:
1
5
2019
medline:
26
11
2019
entrez:
1
5
2019
Statut:
ppublish
Résumé
Platelet Derived Growth Factor Receptor beta (PDGFRβ) has been associated to hepatic stellate cell activation and has been the target of multiple therapeutic studies. However, little is known concerning its use as a diagnostic agent. Circulating PDGFRβ levels were analysed in a cohort of patients with liver fibrosis/cirrhosis due to chronic alcohol abuse, viral hepatitis, or non-alcoholic fatty liver disease (NAFLD). The diagnostic performance of PDGFRβ as individual blood parameter, or in combination with other metabolic factors was evaluated. sPDGFRβ levels are progressively increased with increasing fibrosis stage and the largest difference was observed in patients with significant fibrosis, compared to no or mild fibrosis. The accuracy of sPDGFRβ-levels predicting fibrosis could be increased by combining it with albumin levels and platelet counts into a novel diagnostic algorithm, the PRTA-score, generating a predictive value superior to Fib-4, APRI, and AST/ALT. The sPDGFRβ levels and the PRTA-score are independent of liver disease aetiology, thus overcoming one of the major weaknesses of current non-invasive clinical and experimental scores. Finally, we confirmed the diagnostic value of sPDGFRβ levels and the PRTA-score in an independent patient cohort with NAFLD which was staged for fibrosis by liver biopsy. The PRTA-score is an accurate tool for detecting significant liver fibrosis in a broad range of liver disease aetiologies. FUND: Vrije Universiteit Brussel, the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Flanders) (HILIM-3D; SBO140045), and the Fund of Scientific Research Flanders (FWO).
Sections du résumé
BACKGROUND
BACKGROUND
Platelet Derived Growth Factor Receptor beta (PDGFRβ) has been associated to hepatic stellate cell activation and has been the target of multiple therapeutic studies. However, little is known concerning its use as a diagnostic agent.
METHODS
METHODS
Circulating PDGFRβ levels were analysed in a cohort of patients with liver fibrosis/cirrhosis due to chronic alcohol abuse, viral hepatitis, or non-alcoholic fatty liver disease (NAFLD). The diagnostic performance of PDGFRβ as individual blood parameter, or in combination with other metabolic factors was evaluated.
FINDINGS
RESULTS
sPDGFRβ levels are progressively increased with increasing fibrosis stage and the largest difference was observed in patients with significant fibrosis, compared to no or mild fibrosis. The accuracy of sPDGFRβ-levels predicting fibrosis could be increased by combining it with albumin levels and platelet counts into a novel diagnostic algorithm, the PRTA-score, generating a predictive value superior to Fib-4, APRI, and AST/ALT. The sPDGFRβ levels and the PRTA-score are independent of liver disease aetiology, thus overcoming one of the major weaknesses of current non-invasive clinical and experimental scores. Finally, we confirmed the diagnostic value of sPDGFRβ levels and the PRTA-score in an independent patient cohort with NAFLD which was staged for fibrosis by liver biopsy.
INTERPRETATION
CONCLUSIONS
The PRTA-score is an accurate tool for detecting significant liver fibrosis in a broad range of liver disease aetiologies. FUND: Vrije Universiteit Brussel, the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Flanders) (HILIM-3D; SBO140045), and the Fund of Scientific Research Flanders (FWO).
Identifiants
pubmed: 31036530
pii: S2352-3964(19)30275-0
doi: 10.1016/j.ebiom.2019.04.036
pmc: PMC6558023
pii:
doi:
Substances chimiques
Biomarkers
0
Receptor, Platelet-Derived Growth Factor beta
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
501-512Informations de copyright
Copyright © 2019. Published by Elsevier B.V.
Références
Hepatology. 2000 Sep;32(3):477-81
pubmed: 10960438
Semin Liver Dis. 2001 Aug;21(3):397-416
pubmed: 11586468
Front Biosci. 2002 Aug 01;7:d1720-6
pubmed: 12133817
Am J Gastroenterol. 2002 Oct;97(10):2614-8
pubmed: 12385448
Hepatology. 2003 Aug;38(2):518-26
pubmed: 12883497
Ultrasound Med Biol. 2003 Dec;29(12):1705-13
pubmed: 14698338
Cancer. 1950 Jan;3(1):32-5
pubmed: 15405679
Gastroenterology. 2004 Dec;127(6):1704-13
pubmed: 15578508
J Clin Invest. 2005 Feb;115(2):209-18
pubmed: 15690074
Hepatology. 2005 Jun;41(6):1313-21
pubmed: 15915461
Hepatology. 2006 Jun;43(6):1317-25
pubmed: 16729309
Gastroenterology. 2008 Apr;134(4):960-74
pubmed: 18395077
J Clin Invest. 2010 Jul;120(7):2379-94
pubmed: 20577048
Best Pract Res Clin Gastroenterol. 2011 Apr;25(2):319-33
pubmed: 21497748
BMC Gastroenterol. 2011 Aug 17;11:91
pubmed: 21849046
J Viral Hepat. 2012 Feb;19(2):e212-9
pubmed: 22239521
J Cell Biol. 2013 Feb 18;200(4):373-83
pubmed: 23420871
Curr Pathobiol Rep. 2014 Dec 1;2(4):245-256
pubmed: 25396099
J Hepatol. 2015 Jul;63(1):141-7
pubmed: 25678385
J Hepatol. 2015 Jul;63(1):237-64
pubmed: 25911335
J Hepatol. 2015 Oct;63(4):1038-9
pubmed: 26232376
Hepatology. 2017 May;65(5):1557-1565
pubmed: 28130788
Front Pharmacol. 2017 Feb 09;8:56
pubmed: 28232800
Biomaterials. 2017 Sep;139:91-101
pubmed: 28595132
Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt A):1024-1036
pubmed: 29329986
Radiology. 2018 Mar;286(3):738-763
pubmed: 29461949
Gastroenterology. 1988 Sep;95(3):734-9
pubmed: 3135226
Hepatology. 1994 Jun;19(6):1513-20
pubmed: 8188183
Am J Pathol. 1996 Mar;148(3):785-800
pubmed: 8774134
Hepatology. 1998 May;27(5):1220-6
pubmed: 9581674