F2 and hepatocellular carcinoma: The main possible mechanisms for the production of PIVKA-II by HCC are proposed as follows: (1) increased production of prothrombin precursors [12,13,14,15,16]; (2) decreased activity of γ-glutamyl carboxylase [17,18]; (3) insufficiency of vitamin K [19,20,21]; and (4) a combination of two or more of these factors [1,22,23], although the exact mechanisms still remain to be elucidated.