Analytical and clinical evaluation of a novel ELISA assay for the measurement of serum PIVKA-II in patients with hepatocellular carcinoma of viral-etiology

BACKGROUND: Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin produced by hepatocytes following impaired vitamin K-dependent carboxylase activity. Several studies showed that PIVKA-II could be useful for prognosis prediction in patients with hepatocellular carcinoma (HCC). We aimed to investigate the analytical and clinical performance of a novel enzyme-linked immunosorbent assay (ELISA) for the assessment of PIVKA-II in serum of patients with HCC as compared to a consolidated chemiluminescence enzyme immunoassay (CLEAI) as reference test.METHODS: A total of 103 patients with viral related-HCC (median age: 65 years; males: 74.8%) were retrospectively enrolled. Patients were classified according to Barcelona Clinic Liver Cancer (BCLC) staging system; 67 patients had a diagnosis of early HCC (BCLC 0/A), while 36 had a diagnosis of advanced tumor (BCLC B/C). After HCC diagnosis, patients were followed for a median of 16.8 (7.7-49.2) months. We measured PIVKA-II in serum samples by ELISA (AssayGenie, Dublin, Ireland) and by CLEIA (Fujirebio Inc., Tokyo, Japan) and we investigated the association between PIVKA-II results and overall survival (OS).RESULTS: Overall, the 103 patients examined showed median serum PIVKA-II values of 118 ng/mL and 197 mAU/mL by ELISA and CLEIA, respectively. We observed that PIVKA-II values significantly increased according to BCLC stage (P<0.001) and results from the two methods had a satisfactory correlation (rs=0.84, P<0.001). At multivariate analysis corrected for BCLC stage, both ELISA and CLEIA PIVKA-II resulted significantly and independently associated to OS (HR=2.93, 95% CI: 1.38-6.21, P=0.005 and HR=2.22, 95% CI: 1.15-4.27, P=0.017, respectively).CONCLUSIONS: ELISA and CLEIA PIVKA-II showed good analytical correlation and comparable clinical performance. The new AssayGenie ELISA test could be a valid and cost-effective alternative to CLEIA for measuring serum PIVKA-II in serum of patients with HCC.