Clinical and Experimental Study of Production of Abnormal Prothrombin PIVKA-II in Hepatocellular Carcinoma.

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Fifty-nine percent of patients with hepatocellular carcinoma (HCC) had elevated plasma PIVKA-II levels. None of the cirrhotic patients had elevated pivka-ii levels. Thus PiVKA-II has a high specificity for HCC. There was no correlation between PICKA-II and AFP levels indicating that the combination of these 2 markers seems to be useful in the diagnosis of HCC. There was a correlation between tumor size and PIVKA-II levels in HCC. The half-life of PIVKA-II in HCC patients was 60 hr and was identical to that in vit. K deficiency patients, suggesting that PIVKA-II in HCC patients has the same vit. K sensitivity as that in vit. K deficiency patients. Thus it seems useful to follow HCC patients with PIVKA-II measurement after therapy for its half-life and reduction rate. PIVKA-II was detected in the cultures of 5 hepatoma cell lines and was not detected in non-hepatoma cell lines. There was a marked decrease of PIVKA-II with added vit.K.Thus PIVKA-II is produced by hepatoma cells and its production is dependent on the amount of vit. K available. Using hepatoma cell line huH-2, we found out that all 3 enzymes involved in the production of normal prothrombin, K-epoxide-reductase, K-reductase (vit. K cycle) and -glutamyl-carboxylase, functions in huH-2. The cancerous tissue of HCC patients positive for plasma PIVKA-II showed high PIVKA-II levels and the non-cancreous tissur showed low levels. Prothrombin related antigen levels F-II was higher in cancerous tissue than in non-cancerous tissue. The cancerous tissue of PIVKA-II positive HCC patients showed a more marked F-II staining than in PIVKA-II negative HCC patients. There was postitve PIVKA-II staining in the cancerous tissue of several HCC patients. Thus production of either PIVKA-II or F-II was suggested in hepatoma cell. Is was suggested that increased formation of F-II occurs in HCC, resulting in relative vit. K deficiency and appearance of PIVKA-II.