Background and aims
Liver fibrosis is a pathology of the liver that can result from obesity (NAFLD) or chronic exposure to chronic viral infection and alcohol abuse. An important player in this pathology is the hepatic stellate cell (HSC) which, in response to such injury, will excessively produce and deposit extracellular matrix proteins and gives the affected liver its characteristic rigid state. Till date, the gold standard for diagnosis of liver fibrosis remains the invasive liver biopsy, which is however associated with multiple drawbacks. Experimental and clinical scoring systems based on blood parameters have been developed but lack the sensitivity and specificity to diagnose early onset and progression of the disease. In this study, we identified and evaluated the diagnostic potential of the HSC-specific protein platelet-derived growth factor receptor beta (PDGFRβ).
The study cohort consisted of 148 patients with liver fibrosis/cirrhosis due to various causes of liver injury (NAFLD, alcoholic, viral), and 14 healthy individuals. A validation cohort consisted of 57 patients with non-alcoholic liver disease (NAFLD) who underwent liver biopsy to stage fibrosis. The diagnostic performance of PDGFRβ as individual blood parameter, or in combination with other metabolic factors was evaluated.
We show PDGFRβ to be dominantly expressed by HSCs, as compared to the other liver cell types. In addition, in total liver of murine and human subjects with liver fibrosis and cirrhosis, enhanced PDGFRβ expression is observed, indicating the presence of activated HSCs in the affected liver. Analysis of blood-samples of a human cohort with liver fibrosis/cirrhosis, identified a progressive and stage-dependent elevation of circulating PDGFRβ levels. We show sPDGFRβ-levels to have diagnostic value, as they can significantly distinguish patients with significant fibrosis (F ≥ 2) to those with no or mild fibrosis (F0/1), with an accuracy higher than provided by the use of currently used clinical scores. This accuracy could even be increased by combining it with albumin levels and platelet counts into a novel diagnostic algorithm, which we termed the PRTA-score. Finally, we validated the superior diagnostic capacity of our PRTA-score in an independent patient cohort with NAFLD, which was staged for fibrosis by liver biopsy.
We put forth the PRTA score as an easy applicable, low cost and accurate scoring for significant liver fibrosis.