Protein induced by vitamin K absence or antagonist II: Experience to date and future directions

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with high mortality. The realization of precision medicine in HCC relies upon efficient biomarkers. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an immature prothrombin with insufficient coagulation activity, overexpressing in HCC cells. Previous evidence confirmed the role of PIVKA-II in screening and diagnosing HCC. However, the increased PIVKA-II was observed not only in HCC, but also in non-HCC individuals such as vitamin K deficiency. The joint detection of PIVKA-II and other biomarkers could significantly improve diagnostic accuracy in HCC. Furthermore, PIVKA-II serves as a valuable prognostic predictor, transplantation eligibility, resectability, tumor recurrence, therapeutic efficacy, and malignant tumor behaviors. Additionally, PIVKA-II represents a potential target for agent development to establish new therapeutic strategies. Besides HCC, PIVKA-II also serves as a biomarker of vitamin K status. In this review, we assess the role of PIVKA-II in diagnosis, prediction, and treatment. Over the past decades, substantial progress has been achieved in the application of PIVKA-II. Exploration and innovation are required for further advances in the field of PIVKA-II investigation.