title: Serum soluble urokinase plasminogen activator receptor as a screening test for the early diagnosis of hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Chounta
authors.forename: Christofer
authors.initials: C
authors.lastname: Ellinas
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Tzanetakou
authors.forename: Fani
authors.initials: F
authors.lastname: Pliarhopoulou
authors.forename: Virginia
authors.initials: V
authors.lastname: Mplani
authors.forename: Angelos
authors.initials: A
authors.lastname: Oikonomou
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Leventogiannis
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000453:epidemiology*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000453:epidemiology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D055293:Receptors, Urokinase Plasminogen Activator
keywords: early diagnosis; hepatocellular carcinoma; suPAR