Serum soluble urokinase plasminogen activator receptor as a screening test for the early diagnosis of hepatocellular carcinoma

Abstract

Background & Aims: Early detection of hepatocellular carcinoma (HCC) before imaging signs appear remains an unmet medical need. Former publications suggest that soluble urokinase plasminogen activator receptor (suPAR) is a non-specific cancer marker. suPAR was validated for the detection of patients at risk for HCC. Methods: After an initial training set in 23 patients with extreme disease phenotypes, a prospective test set was conducted in which 267 patients without any imaging signs of HCC were followed up for 7 years. Patients were divided into low risk and high risk for the development of HCC by the EASL criteria. suPAR was measured at the beginning of follow-up. All patients underwent liver biopsy to define staging of fibrosis. The primary study endpoint was to define a cut-off among high-risk patients by the EASL criteria that can early discriminate those at real risk for HCC. Results: The training set showed that suPAR was significantly greater in patients with HCC even in the absence of underlying cirrhosis compared with patients with minimal liver inflammation because of fatty deposition. The test set showed that among the high-risk EASL subgroup, suPAR more than 9.56 ng/ml had sensitivity 76.0%, specificity 90.4%, positive predictive value 54.3% and negative predictive value 96.2% for the development of HCC (odds ratio: 29.88, P < 0.0001). In survival analysis, patients with suPAR above 9.56 ng/ml at baseline progressed earlier to HCC. Conclusions: The specificity and negative predictive value make serum suPAR a potential screening tool for the early detection of HCC in patients with chronic liver disorders. © 2014 John Wiley & Sons A/S