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.1,2

 

Hepatocellular carcinoma (HCC)1,2

 

Hepatocellular carcinoma (HCC) constitutes a major global health problem. HCC is the 5th most common cancer worldwide and the most common primary liver malignancy and is the 3rd leading cause of cancer-related death worldwide: it accounts for more than 90 % of primary liver cancer.3,4,5 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.6 Survival is poor in most patients with HCC (5-year survival less than 5%) except in patients in the early stage who receive potentially curative therapy (liver transplant, surgical resection, or ablation), where a considerable improvement in survival has been observed (5-year survival ranges between 40% and 70%).7

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.8,9 PIVKA‑II is a precursor and abnormal form of prothrombin which was found originally in patients with hepatitis and cirrhosis.9 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.10,11In 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.12

 

 

References

 

  1. Elecsys® PIVKA-II Method Sheet for material #08333602190 for cobas e 411, cobas e 601 & cobas e 602
  2. Elecsys® PIVKA-II Method Sheet for material #08333629190 for cobas e 801
  3. GLOBOCAN 2020. Cancer fact sheets - all cancers . Available at https://gco.iarc.fr/today/home assessed June 2021
  4. 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.
  5. Llovet, J.M. et al. (2016). Hepatocellular carcinoma. Nat Rev Dis Prim 14(2), 16018.
  6. El-Seraq, H.B. (2012). Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma. Gastroenterology 142(6), 1264-1273.
  7. El-Sareg HB. Surveillance for hepatocellular carcinoma: in whom and how? Therap Adv Gastroenterol 2011; 4(1): 5–10; doi: 10.1177/1756283X10385964
  8. 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.
  9. 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.
  10. 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.
  11. Seo et al. Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol. 2015 Apr 7; 21(13): 3928–3935. doi: 10.3748/wjg.v21.i13.3928
  12. Saitta et al. PIVKA-II is a useful tool for diagnostic characterization of ultrasound-detected liver nodules in cirrhotic patients. Medicine 2017 Jun; 96(26): e7266. doi: 10.1097/MD.0000000000007266

Elecsys® PIVKA-II1,2

  • Systems

    cobas e 411 analyzer, cobas e 601 / cobas e 602 modules, cobas e 801 analytical unit, cobas e 402 analytical unit

  • 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 analytical unit, cobas e 402 analytical unit

  • Onboard stability

    8 weeks on cobas e 411 analyzer and cobas e 601 / cobas e 602 modules
    16 weeks on cobas e 801 analytical unit, cobas e 402 analytical unit

  • Measuring range

    3.5 – 12,000 ng/mL

  • Limit of Detection (LoD)

    cobas e 411 analyzer, cobas e 601 / cobas e 602 modules: ≤ 3.5 ng/mL
    cobas e 801 analytical unit, cobas e 402 analytical unit: ≤ 3.5 ng/mL

  • Limit of Quantitation (LoQ)

    cobas e 411 analyzer, cobas e 601 / cobas e 602 modules: ≤ 4.5 ng/mL
    cobas e 801 analytical unit, cobas e 402  analytical unit: ≤ 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 3.7 – 4.3 %
    cobas e 801 analytical unit, cobas e 402 analytical unit: CV 4.2 – 6.9 %

  • Repeatability in positive samples*

    cobas e 411 analyzer: CV 1.7 - 2.6 %
    cobas e 601 / cobas e 602 modules: CV 1.6 – 2.2 %
    cobas e 801 analytical unit, cobas e 402 analytical unit: CV 1.0 – 1.5 %

     

     

     

     

     

     

     

* Human samples only