PIVKA-II combined with alpha-fetoprotein for the diagnostic value of hepatic tumors in children: a multicenter, prospective observational study

To investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors. A multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP. The mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone. The serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance. Clinical Trials, NCT03645655. Registered 20 August 2018, https://www.clinicaltrials.gov/ct2/show/NCT03645655 .