Elecsys® PIVKA-II

Immunoassay for the quantitative measurement of protein induced by vitamin K absence or antagonist-II (PIVKA‑II)

Elecsys PIVKA-II

Immunoassay for the quantitative measurement of protein induced by vitamin K absence or antagonist-II (PIVKA‑II)

Elecsys® PIVKA-II is an immunoassay for the quantitative measurement of protein induced by vitamin K absence or antagonist-II (PIVKA‑II) in human serum and plasma. The assay is used as an aid in the diagnosis of hepatocellular carcinoma (HCC). The results must be interpreted in conjunction with other methods in accordance with standard clinical management guidelines.

 

Hepatocellular carcinoma (HCC)

 

Hepatocellular carcinoma (HCC) constitutes a major global health problem. HCC is the 6th most common cancer worldwide and the most common primary liver malignancy and is a leading cause of cancer-related death worldwide: it accounts for more than 90 % of primary liver cancer.1,2,3 It is the 2nd most common cause of death from cancer in males and the 6th in females worldwide. Major risk factors of developing HCC are infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) as indicated by the strong correlation between the prevalence of HCC and chronic hepatitis B and C.4 HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages.5 Early diagnosis and intervention can thus significantly improve survival.6

Protein induced by vitamin K or antagonist-II (PIVKA-II; also known as des-γ-carboxy prothrombin [DCP]) has been identified as a promising biomarker with utility in the surveillance, diagnosis, and management of HCC.7 PIVKA‑II is a precursor and abnormal form of prothrombin which was found originally in patients with HCC.8 In the absence of vitamin K or the presence of its antagonist inhibiting vitamin K-dependent carboxylase activity, PIVKA-II is generated with a loss of coagulation activity.9 In neoplastic cells of HCC, PIVKA-II is thought to be produced as consequence of an acquired defect of post-translational carboxylation of prothrombin’s precursor.

 

 

Elecsys® PIVKA-II

Elecsys® PIVKA-II

  • Systems

    cobas e 411 analyzer, cobas e 601 / cobas e 602 modules, cobas e 801 module

  • Testing Time

    18 minutes

  • Test principle

    One-step double antigen sandwich assay

  • Calibration

    2-point

  • Sample material

    Serum collected using standard sampling tubes or tubes containing separating gel; Li-heparin, K2-EDTA and K3-EDTA plasma; Li-heparin plasma tubes containing separating gel

  • Sample volume

    40 μL cobas e 411 analyzer, cobas e 601 / cobas e 602 modules
    24 μL cobas e 801 module

  • Onboard stability

    8 weeks on cobas e 411 analyzer and cobas e 601 / cobas e 602 modules
    16 weeks on cobas e 801 module

  • Measuring range

    3.5 – 12,000 ng/mL

  • Limit of Detection (LoD)

    ≤ 3.5 ng/mL

  • Limit of Quantitation (LoQ)

    ≤ 4.5 ng/mL

  • Intermediate precision in positive samples

    cobas e 411 analyzer: CV 5.0 – 6.2 %
    cobas e 601 / cobas e 602 modules: CV 3.4 – 4.3 %
    cobas e 801 module: CV 4.2 – 6.9 %

  • Repeatability in positive samples

    cobas e 411 analyzer: CV 1.5 -2.9 %
    cobas e 601 / cobas e 602 modules CV 1.4 – 2.2 %
    cobas e 801 module CV 1.0 – 1.8 %

References

 

  1. Ferlay, J. et al. (2012). GLOBOCAN v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 Internet. Available at: http://globocan.iarc.fr.
  2. Fitzmaurice C. et al. (2017). The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: Results from the Global Burden of Disease Study 2015. JAMA Oncol 3, 1683-1691.
  3. Llovet, J.M. et al. (2016). Hepatocellular carcinoma. Nat Rev Dis Prim 14(2), 16018.
  4. El-Seraq, H.B. (2012). Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma. Gastroenterology 142(6), 1264-1273.
  5. Schafer, D.F., Sorrell, M.F. (1999). Hepatocellular carcinoma. Lancet 353, 1253-7.
  6. Bruix, J., Sherman, M. (2005). Management of hepatocellular carcinoma. Hepatology 42, 1208-1236.
  7. Choi, J.Y. (2013). Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J. Gastroenterol 19(3), 339-346.
  8. Liebmann, H.A. et al. (1984). Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Eng J Med 310, 1427-1431.
  9. Ono, M. et al. (1990). Measurement of immunoreactive prothrombin precursor and vitamin-K-dependent gamma-carboxylation in human hepatocellular carcinoma tissues: Decreased carboxylation of prothrombin precursor as a cause of des-gamma-carboxy prothrombin synthesis. Tumour Biol 11, 319-326.