A PDGFRβ-based score predicts significant liver fibrosis in patients with chronic alcohol abuse, NAFLD and viral liver disease.
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
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
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
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).
['Lambrecht|Joeri|J|', 'Verhulst|Stefaan|S|', 'Mannaerts|Inge|I|', 'Sowa|Jan-Peter|JP|', 'Best|Jan|J|', 'Canbay|Ali|A|', 'Reynaert|Hendrik|H|', 'van Grunsven|Leo A|LA|']
D000328:Adult D000465:Algorithms D000818:Animals D015415:Biomarkers D001706:Biopsy D056486:Chemical and Drug Induced Liver Injury D004195:Disease Models, Animal D042783:Endothelial Cells D000067128:Extracellular Vesicles D005235:Fatty Liver, Alcoholic D005260:Female D055166:Hepatic Stellate Cells D006524:Hepatitis, Viral, Animal D006801:Humans D008103:Liver Cirrhosis D008297:Male D051379:Mice D008875:Middle Aged D065626:Non-alcoholic Fatty Liver Disease D012372:ROC Curve D020797:Receptor, Platelet-Derived Growth Factor beta D015203:Reproducibility of Results D012680:Sensitivity and Specificity
Platelet derived growth factor receptor Hepatic stellate cell Biomarker Diagnosis Extracellular vesicle