Protein Induced by Vitamin K Absence or Antagonist II in Primary Liver Cancer: Basic Research Insights and Clinical Applications.

Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer and continues to be a major cause of cancer-related mortality, particularly in regions of China with a high hepatitis B virus prevalence. Early-stage diagnosis remains challenging due to its asymptomatic onset and the limited sensitivity of conventional biomarkers, which together contribute to delayed detection, suboptimal therapeutic outcomes, and poor prognosis. These limitations underscore the urgent need for reliable, sensitive, and specific biomarkers to enable timely detection and targeted intervention. Protein induced by vitamin K absence or antagonist-II, an abnormal prothrombin variant generated under vitamin K deficiency or antagonism, has emerged as a promising candidate with diagnostic and therapeutic relevance in HCC. This review critically examines the molecular and biological characteristics of protein induced by vitamin K absence or antagonist-II, evaluates its clinical utility in HCC diagnosis and management, and delineates the current limitations hindering its broader application. Furthermore, future perspectives are proposed to guide translational research and clinical implementation. Collectively, this review aims to provide a comprehensive theoretical framework to advance precision diagnosis and individualized treatment strategies for HCC.