Production of abnormal prothrombin (PIVKA-II) by hepatocellular carcinoma. A clinical and experimental study.

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We measured plasma abnormal prothrombin PIVKA-II levels in normal subjects and in patients with hepatocellular carcinoma (HCC) and various diseases by the enzyme immunoassay according to the enzyme-linked immunosorbent assay developed by Motohara. Fifty-eight percent of 52 patients with HCC had significantly elevated PIVKA-II levels. By contrast, 50 normal controls, 13 pregnant women and 10 patients with acute hepatitis had normal levels. Three of 55 patients with chronic liver disease, and 6 of 32 with other malignancies showed a slight increase. Thus, increased plasma PIVKA-II seems to be specific for HCC.<BR>To elucidate the mechanism for the increase of PIVKA-II in HCC, we cultured a human hepatoma cell line, huH-2, and measured the levels of this abnormal prothrombin in the medium. The huH-2 cells produced large amounts of PIVKA-II into the medium without added vitamin K. It increased in a cell concentration and time-dependent fashion. These cells produced no detectable amount of PIVKA-II in the medium with added vitamin K.<BR>Thus, human hepatoma cell line huH-2 produces PIVKA-II and its production is dependent on the amount of vitamin K available in the medium. PIVKA-II may be a useful tumor marker for the clinical diagnosis of HCC.
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