Diagnostic specificity and sensitivity of PIVKAII, GP3, CSTB, SCCA1 and HGF for the diagnosis of hepatocellular carcinoma in patients with alcoholic liver cirrhosis

Ann Clin Biochem. 2018 May;55(3):355-362. doi: 10.1177/0004563217726808. Epub 2017 Sep 20.


Introduction Despite some new treatment possibilities, the improvement in survival rate for hepatocellular carcinoma (HCC) patients is still poor due to late diagnosis. The aim of this study was to investigate the diagnostic sensitivity and specificity of protein induced by vitamin K absence or antagonist-II (PIVKAII), Glypican-3 (GP3), Cystatin B (CSTB), squamous cell carcinoma antigen 1 (SCCA1) and hepatocyte growth factor (HGF) as potential tumour markers for HCC in patients with alcoholic liver cirrhosis (ALC) using imaging techniques (MSCT and MRI) as reference standards. Patients and methods Eighty-three participants were included: 20 healthy volunteers, 31 patients with ALC and 32 patients with HCC. Peripheral blood sampling was performed for each participant, and serum concentrations of PIVKAII, GP3, CSTB, SCCA1 and HGF were determined using commercial ELISA kits. Results Only serum concentrations of PIVKAII were significantly higher in HCC patients as compared with ALC and healthy controls (cut-off: 2.06 µg/L; AUC: 0.903), whereas individual diagnostic performance of other individual compounds was inadequate. The 'best' combination of tumour markers in our study includes all tested markers with AUC of 0.967. Conclusion While novel diagnostic tumour markers are urgently needed, the examined potential tumour markers, with the exception of PIVKAII seem to be inadequate for diagnosing HCC in ALC. Furthermore, probably the future is in finding the best optimal combination of tumour markers for diagnosing HCC based on cost-effectiveness.

Keywords: Tumour markers; cancer; liver disease.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism*
  • Area Under Curve
  • Biomarkers / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / enzymology
  • Case-Control Studies
  • Cystatin B / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glypicans / metabolism*
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Liver Cirrhosis, Alcoholic / blood
  • Liver Cirrhosis, Alcoholic / complications*
  • Liver Neoplasms / blood
  • Liver Neoplasms / complications
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / enzymology
  • Male
  • Middle Aged
  • Protein Precursors / metabolism*
  • Prothrombin / metabolism*
  • Sensitivity and Specificity
  • Serpins / metabolism*
  • Survival Rate


  • Antigens, Neoplasm
  • Biomarkers
  • Biomarkers, Tumor
  • CSTB protein, human
  • GPC3 protein, human
  • Glypicans
  • HGF protein, human
  • Protein Precursors
  • Serpins
  • squamous cell carcinoma-related antigen
  • acarboxyprothrombin
  • Hepatocyte Growth Factor
  • Cystatin B
  • Prothrombin