Title : Protein induced by vitamin K absence (PIVKA-II) in the hepatocellular carcinoma (HCC) diagnostics
Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Its survival rate does not exceed 15 %. The prevalence rates differ based on ethnicity. Higher rates are observed in Asian countries, but its incidence rate has been increasing in the US and Europe during last years. Its mortality is almost equal to its morbidity. Carcinogenesis of HCC is multifactorial and includes a previous infection with Hepatitis B or C viruses (HBV, HCV), aflatoxin B or alcohol consumption resulting in liver cirrhosis. New cancer sometimes develops with no previous link to the above mentioned agents, sometimes non-alcoholic steatohepatitis (NASH) in diabetic patients has been associated with liver cancer.
Aim: The aim of this pilot study was to evaluate the clinical contribution of the new biomarker protein induced by vitamin K absence (PIVKA-II) for HCC diagnostics and compare it with the alpha-fetoprotein (AFP), a tumour marker routinely used in clinical practice. Methods: A total 332 patients were enrolled into this study. The major cancer group with HCC includes 64 patients. All clinical stages were included, but advanced stages were more frequent. The second group contains 48 patients with liver metastases of colorectal cancer origin. The third group of patients with benign liver diseases includes 42 patients with liver cirrhosis resulting mostly from previous alcohol intake. The control group consists of 178 healthy individuals. Serum samples were collected at the time of the diagnosis prior to any kind of therapy.
Results: PIVKA-II and AFP achieved the highest serum levels in the group of HCC patients and the lowest levels in the control group. The optimal cut-off values at 95% specificity are shown in Table III for both biomarkers. We established individual cut-off values for each assessed group. In general, PIVKA-II achieved much better clinical sensitivity than AFP and the difference in this sensitivity was statistically significant in all comparisons. The PIVKA-II sensitivities varied over the ranges 89.1% - 96.9%. PIVKA-II achieved the best sensitivity (96.9%) when distinguishing between the HCC and control groups with the proposed cut-off values 60 mAU/ml. The AFP sensitivities varied over the ranges 34.3% - 50.0%. AFP achieved the best sensitivity (50.0%) in distinguishing between the HCC group and the group with metastatic colorectal cancer with the proposed cut-off values 6 ng/ml.
Conclusion: Newly tested PIVKA-II achieved better parameters of sensitivity in our pilot study than AFP - a traditionally used HCC tumour marker. We can recommend adding PIVKA-II to the routine panel of HCC tumour markers.