Clinical evaluation of plasma des-γ-carboxy prothrombin as a marker protein of hepatocellular carcinoma in patients with tumors of various sizes

Abstract

We measured des-γ-carboxyprothrombin (DCP) (prothrombin induced by vitamin K absence or antagonist-II, abbreviated as PIVKA-II) by a newly developed enzyme immunoassay using an anti-DCP monoclonal antibody in 665 human subjects, of which 112 were patients with hepatocellular carcinoma (HCC). PIVKA-II was elevated to more than 0.1 AU/ml in 54 of the 112 patients (48.2%) with HCC, while it was positive only in 7.1% of those with liver cirrhosis and 3.1% of those with chronic hepatitis. Three patients with elevated PIVKA-II greater than 0.1 AU/ml who had been diagnosed as having liver cirrhosis by ultrasonography and computed tomography at the start of this study developed a diffuse type of HCC three or six months later, which was detected by angiography. No obvious correlation was observed between plasma PIVKA-II concentration and serum α-fetoprotein (AFP) level in HCC patients. Of the 112 HCC patients, 40.2% showed an increase in AFP to above 200 ng/ml. In the remaining patients, 32.8% had a PIVKA-II concentration greater than 0.1 AU/ml. In these patients with a negative or low serum AFP concentration, PIVKA-II proved to be a valuable tumor marker for laboratory diagnosis of HCC. Among them, 59.8% tested positive for PIVKA-II and/or AFP. Thus, combination assay with PIVKA-II and AFP seems useful for increasing the accuracy of laboratory diagnosis of HCC. None of patients with a solitary tumor smaller than 2 cm had elevated PIVKA-II. In patients with larger-sized and multiple HCC, positive results of elevated PIVKA-II were more frequent than those of increased AFP. Thus, the determination of PIVKA-II may be more useful than AFP assay in patients with larger-sized and multiple tumors. The levels of plasma PIVKA-II concentration were higher in patients with larger-sized and multiple tumors than in those with smaller ones. In 20 patients, PIVKA-II decreased significantly after transcatheter arterial embolization (TAE) therapy, and in eight of these 20 patients it normalized after TAE. In conclusion, plasma PIVKA-II might be used as a valuable marker for the diagnosis and screening of HCC, especially in patients with negative or low AFP and in those with larger-sized and multiple tumors. However, its usefulness for mass screening of small HCC is limited.