Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion

J Hepatol. 2015 Apr;62(4):848-54. doi: 10.1016/j.jhep.2014.11.005. Epub 2014 Nov 11.

Abstract

Background & aims: Prothrombin induced by vitamin K absence-II (PIVKA-II) is a diagnostic and surveillance marker for HCC mainly used in Asia, and has also been shown to be a predictor of microvascular invasion (MVI), a major prognostic factor in HCC. However, experience with PIVKA-II in Europe remains limited.

Methods: In a French cohort, we conducted a case-control study to compare the performances of α-fetoprotein (AFP) and PIVKA-II serum levels for diagnosis of early stage HCC, and we determined the value of PIVKA-II serum and tissue expression in pre-operative detection of MVI. 43 cirrhotic control patients and 85 HCC cases were included, of which 54 (63.5%) had early stage HCC (n=22 very early, n=32 early). PIVKA-II tissue expression was assessed by immunohistochemistry in HCC surgical samples.

Results: For the diagnosis of early HCC, PIVKA-II had a sensitivity of 77% and a specificity of 82% at a cut-off of 42 mAU/ml, vs. 61% and 50% for AFP at a cut-off of 5.5 ng/ml (AUC 0.81 vs. 0.58, respectively). A PIVKA-II level >90 mAU/ml was an independent predictor of MVI (HR 3.5; 95% CI 1.08-11.8; p=0.043). High PIVKA-II tissue expression was significantly associated with the presence of MVI (p=0.001). When combining PIVKA-II immunostaining with the PIVKA-II serum level, sensitivity and specificity for the diagnosis of MVI increased from 70% to 87% and 63% to 90%, respectively.

Conclusions: PIVKA-II was more efficient than AFP for the diagnosis of early HCC, and could be used as a predictive biomarker of MVI.

Keywords: Alpha fetoprotein; Diagnosis; Hepatocellular carcinoma; Microvascular invasion; Prothrombin induced by vitamin K absence-II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers* / blood
  • Biomarkers* / metabolism
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / pathology
  • Case-Control Studies
  • Comparative Effectiveness Research
  • Early Detection of Cancer
  • Female
  • France
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / diagnosis*
  • Predictive Value of Tests
  • Prognosis
  • Protein Precursors* / blood
  • Protein Precursors* / metabolism
  • Prothrombin* / metabolism
  • ROC Curve
  • Sensitivity and Specificity
  • alpha-Fetoproteins / metabolism*

Substances

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