bwge2019

Authors
J. LAMBRECHT (1), S. VERHULST (1), I. MANNAERTS (1), J. SOWA (2), J. BEST (2), A. CANBAY (2), H. REYNAERT (1), L. VAN GRUNSVEN (1) / [1] Vrije Universiteit Brussel (VUB), Jette, Belgium, Department of Basic Biomedical Sciences, Liver Cell Biology Laboratory, [2] University Hospital Magdeburg, , Germany, Department of Gastroenterology, Hepatology and Infectious Diseases
Introduction
Diagnosis of liver fibrosis onset and regression remains a controversial subject in the current clinical setting, as the gold standard remains the invasive liver biopsy. Multiple novel non-invasive markers have been proposed but lack sufficient sensitivity and specificity for diagnosis of early stage liver fibrosis. 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.
Aim
In this study, we analysed the diagnostic potential of PDGFRβ for liver fibrosis in a heterogenous patient population.
Methods
The study cohort consisted of 148 patients with liver fibrosis/cirrhosis due to various causes of liver injury (metabolic, alcoholic, viral), and 14 healthy individuals as control population. A validation cohort of 57 patients with metabolic liver disease, who underwent liver biopsy to stage fibrosis, were gathered. Circulating soluble PDGFRβ (sPDGFRβ) levels were determined using a commercial ELISA kit. The diagnostic performance of sPDGFRβ as individual parameter, or in combination with other biochemical and metabolic factors was evaluated, and values were compared to those obtained by the clinical diagnostic algorithms Fib-4, APRI, and AST/ALT ratio.
Results
In the total patient population, sPDGFRβ levels were progressively augmented with increasing fibrosis stage. Circulating sPDGFRβ levels were elevated (p < 0.0001) in patients with significant fibrosis (F ≥ 2), compared to no or mild fibrosis (F0/1), with a discriminative capacity, as quantified by AUC, of 0.7303, which was shown to be higher for this cohort than the AUCs of Fib-4, APRI, and AST/ALT ratio. The accuracy of sPDGFRβ could be increased by combining it with albumin levels and platelet counts into a novel diagnostic algorithm, which we termed the PRTA-score. Using a cut-off value of 7.804; a sensitivity of 77.11% and a specificity of 73.17% could be obtained for the diagnosis of significant fibrosis (F ≥ 2). AUC values for the prediction of advanced liver fibrosis (F ≥ 3) and cirrhosis (F = 4) were respectively 0.7470 and 0.7995; values which are slightly better, or comparable to Fib-4, APRI, and AST/ALT ratio. The diagnostic value of sPDGFRβ levels and the PRTA score were confirmed in an independent patient cohort, suffering from metabolic liver disease, which were staged for fibrosis by liver biopsy.
Conclusions
We put forth the PRTA score as an easy applicable, low cost and accurate scoring for significant liver fibrosis. With validation in larger patient cohorts, this serological test could become an important tool in future non-invasive clinical assessment of liver fibrosis.