Utility of the PIVKA II biomarker as a tool for early detection of hepatocarcinoma

Utilidad del biomarcador PIVKA II como herramienta de  detección temprana de hepatocarcinoma

Hepatocellular carcinoma is the most common liver neoplasm and one of the leading causes of cancer mortality worldwide. Early detection is crucial to improve prognoses and survival, yet most patients are diagnosed at advanced tumor stages, resulting in the loss of valuable treatment opportunities. Despite the standardized use of imaging such as biannual ultrasound and alpha-fetoprotein measurement, screening remains suboptimal. Therefore, PIVKA-II has been proposed as a clinically useful biomarker in early diagnosis, even in the context of negative alpha-fetoprotein measurement, with high sensitivity and specificity for detection of small tumors and high discriminatory ability for differentiating hepatocellular carcinoma of viral or metabolic etiology. PIVKA-II is an anomalous form of prothrombin, with absence of γ-carboxylation on one or more of its glutamic acid residues,altering its interaction with other factors of the coagulation cascade. This post-translational modification is favored by a decrease in the enzymatic activity of γ-glutamyl carboxylase in the context of the tumor microenvironment. Multiple controversies arise regarding the optimal cut-off values for screening, the most appropriate measurement methods and its diagnostic performance in isolation or in combination with other biomarkers.