Background:We aimed to investigate whether the protein induced by the vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors.Methods: A multicenter prospective observational study was performed at nine regional institutions around China from October 1, 2018 to September 30, 2020, and a total of 257 eligible patients were enrolled. Children with confirmed hepatic masses were placed in the test group (Group T, n=144) and divided into the hepatoblastoma group (Group THB, n=98) and the hemangioendothelioma group (Group THE, n=46), and children with extrahepatic abdominal masses were placed in the control group (Group C, n=113). Peripheral blood was collected from each patient prior to surgery or chemotherapy. Receiver operating characteristic (ROC) curves and area under the curve (AUROC) were used to evaluate the diagnostic and differential diagnostic efficiency.Results:The mean levels of PIVKA-II and AFP were both significantly higher in Group T than in Group C (P=0.001, P＜0.001) and in Group THB than in Group THE (P=0.018, P=0.013). For the diagnosis performance, PIVKA-II had a sensitivity of 86.7% and a specificity of 81.3% at a cutoff of 32.6 mAU/ml vs. 84.1% and 81.8% for AFP at a cutoff of 120 ng/ml (AUROC 0.867 vs. 0.857, respectively). The combination of PIVKA-II and AFP had higher sensitivity (88.5%), specificity (84.7%) and AUROC (0.891) than PIVKA-II or AFP alone. The differential diagnostic value of PIVKA-II and AFP in differentiating hepatoblastoma from hemangioendothelioma was further assessed. PIVKA-II had a sensitivity of 71.7% and a specificity of 88.7% at a cutoff of 47.1 mAU/ml, and there was 63.0% and 78.6% of AFP at a cutoff of 560 ng/ml (AUROC 0.876 vs. 0.743, respectively). The combined markers also showed a higher sensitivity (72.7%), a higher specificity (91.8%) and a higher AUROC (0.895) than PIVKA-II or AFP alone.Conclusions:The serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. PIVKA-II had superior sensitivity and specificity in the diagnosis of childhood hepatic tumors. The combination of PIVKA-II and AFP further increased the diagnostic performance.Trial registration: Clinical Trials, NCT03645655. Registered 20 August 2018, https://www.clinicaltrials.gov/ct2/show/NCT03645655
