Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients

Scand J Gastroenterol. 2016 Oct;51(10):1257-62. doi: 10.1080/00365521.2016.1183705. Epub 2016 May 26.

Abstract

Objective: As a marker for Hepatocellular Carcinoma (HCC), Protein Induced by Vitamin K Absence II (PIVKA-II) seems to be superior to alpha fetoprotein (AFP). To better characterize the role of PIVKA-II, both AFP and PIVKA-II have been measured in Italian patients with diagnosis of HCC compared with patients affected by non-oncological liver pathologies.

Materials and methods: Sixty serum samples from patients with HCC, 60 samples from patients with benign liver disease and 60 samples obtained from healthy blood donors were included in the study. PIVKA-II and AFP were measured by LUMIPULSE(®) G1200 (Fujirebio-Europe, Belgium). We considered as PIVKA-II cutoff 70 mAU/ml (mean +3SD) of the values observed in healthy subjects.

Results: The evaluation of PIVKA-II showed a positivity of 70% in patients with HCC and 5% in patients with benign diseases (p < 0.0001) whereas high levels of AFP were observed in 55% of HCC patients and in 47% of patients with benign diseases. The combined Receiver Operating Characteristic (ROC) analysis of the two analytes revealed a higher sensitivity (75%) compared to those observed for the individual biomarkers. In conclusion, we demonstrate that as a marker for HCC, PIVKA-II is more specific for HCC and less prone to elevation during chronic liver diseases.

Conclusions: The combination of the two biomarkers, evaluated by the ROC analysis, improved the specificity compared to a single marker. These data suggest that the combined analysis of the two markers could be a useful tool in clinical practice.

Keywords: AFP; PIVKA-II; benign liver diseases; hepatocellular carcinoma; tumor marker.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood*
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / pathology
  • Case-Control Studies
  • Female
  • Humans
  • Italy
  • Liver Neoplasms / blood*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Protein Precursors / blood*
  • Prothrombin
  • ROC Curve
  • Sensitivity and Specificity
  • Young Adult
  • alpha-Fetoproteins / analysis*

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • Protein Precursors
  • alpha-Fetoproteins
  • acarboxyprothrombin
  • Prothrombin