vitamin-k-semiquinone-radical and Hepatitis--Chronic

Topics: Chromatography, High Pressure Liquid; Hepatitis, Chronic; Humans; Indicators and Reagents; Liver; Liver Cirrhosis; Reference Values; Vitamin K; Vitamin K 1

Des-gamma-carboxy prothrombin [DCP], a protein induced by vitamin K absence or antagonist-II and also abbreviated PIVKA-II, was evaluated as a serologic marker for hepatocellular carcinoma (HCC). Its plasma levels were measured by enzyme immunoassay (E-1023) using an anti-DCP monoclonal antibody in 514 patients with various diseases. Of 120 patients with HCC, 76 (63%) had abnormal DCP levels greater than 0.1 arbitrary unit (AU)/ml and 58 (48%) showed levels greater than 0.3 AU/ml. When a diagnostic minimum level of 0.3 AU/ml was applied for DCP, false-positive cases of HCC were virtually eliminated. In some patients with HCC, plasma DCP levels normalized after surgical resection of the tumor. However, they rose again later with recurrence of the disease. The sensitivity of DCP in the diagnosis and monitoring of HCC was increased by serial and simultaneous determinations of alpha-fetoprotein (AFP), because high DCP levels were observed more often in low AFP-producing HCC patients. Elevated plasma DCP levels were not related to low vitamin K concentration in the serum. In fact, in many patients vitamin K administration resulted in only a moderate reduction of DCP levels. These results suggested strongly that DCP was synthesized by the hepatoma cells.

Topics: Adenoma, Bile Duct; alpha-Fetoproteins; Antibodies, Monoclonal; Biomarkers; Carcinoma, Hepatocellular; Female; Hepatitis, Chronic; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Male; Neoplasm Proteins; Neoplasms; Protein Precursors; Prothrombin; Vitamin K

The clinical usefulness of plasma abnormal prothrombin, defined as a protein induced by vitamin K absence or antagonist-II: PIVKA-II, as a tumor marker for hepatocellular carcinoma (HCC), was evaluated. Plasma PIVKA-II concentration was determined by an enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody specific for PIVKA-II. Forty-one (65%) out of 63 patients with HCC had an abnormal PIVKA-II level above 0.13 arbitrary units (AU)/ml; the level was above 0.3 AU/ml in 33 patients (52%) and above 0.5 AU/ml in 27 patients (43%). On the other hand, most of the 282 patients with various liver diseases other than HCC had normal or slightly elevated levels of PIVKA-II. Their values were all below 0.5 AU/ml, with the exception of 2 patients with decompensated liver cirrhosis. The patients with PIVKA-II values above 0.5 AU/ml were strongly suspected of having HCC. Plasma PIVKA-II levels were not related to serum alpha-fetoprotein (AFP) levels, but were above 0.5 AU/ml in 14 (44%) out of the 32 patients whose serum AFP levels were below 400 ng/ml. In some patients with HCC, PIVKA-II was increased throughout the course of the disease, and in others it normalized after surgical resection of the tumor. We conclude that the plasma PIVKA-II assay by the ELISA method using a monoclonal antibody is a useful diagnostic tool for monitoring HCC, particularly in HCC patients with low AFP levels.

Topics: Adenoma, Bile Duct; alpha-Fetoproteins; Antibodies, Monoclonal; Biomarkers; Carcinoma, Hepatocellular; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis, Chronic; Humans; Liver Diseases; Liver Neoplasms; Male; Protein Precursors; Prothrombin; Vitamin K