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Liver fibrosis is the result of persistent liver injury, and is characterized by sustained scar formation and disruption of the normal liver architecture. The extent of fibrosis is considered as an important prognostic factor for the patient outcome, as an absence of (early) treatment can lead to the development of liver cirrhosis and hepatocellular carcinoma. Till date, the most sensitive and specific way for the diagnosis and staging of liver fibrosis remains liver biopsy, an invasive diagnostic tool, which is associated with high costs and discomfort for the patient. Over time, non-invasive scoring systems have been developed, of which the measurements of serum markers and liver stiffness are validated for use in the clinic. These tools lack however the sensitivity and specificity to detect small changes in the progression or regression of both early and late stages of fibrosis. Novel non-invasive diagnostic markers with the potential to overcome these limitations have been developed, but often lack validation in large patient cohorts. In this review, we will summarize novel trends in non-invasive markers of liver fibrosis development and will discuss their (dis-)advantages for use in the clinic.

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).