BACKGROUND/AIMS: Prothrombin induced by Vitamin K Antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) subtype reacting with Lens Culinaris Agglutinin (AFP-L3) are known as specific tumor markers for HCC. Recently a more sensitive EIA method for PIVKA-II and an automatic analyzer with Liquid Phase Binding Assay method (LBA method) for AFP-L3 have been developed. The aim of this study was to evaluate the feasibility of PIVKA-II and AFP-L3 measured by newly developed methods as complementary tumor markers to AFP in the diagnosis of HCC. METHODS: The serum concentration of AFP, PIVKA-II, and a fraction of AFP-L3 were determined from 188 patients with HCC and 118 patients with various liver diseases including 46 with liver cirrhosis, 10 with chronic hepatitis, 50 with metastatic liver cancers, and 12 with benign tumors of the liver. AFP was measured by EIA, PIVKA-II by sensitive EIA, and AFP-L3 by the LBA method with LiBASys Auto-analyzer. The cutoff values for AFP, PIVKA-II, and AFP-L3 were 400 ng/mL, 40 mAU/mL, and 15%, respectively. RESULTS: The sensitivity and specificity of serum PIVKA-II were 69.2% and 76.5%, respectively. Sixty-two (51.2%) of 121 patients with HCC, in which AFP was less than 400 ng/mL were PIVKA-II positive. The sensitivity and specificity of serum AFP-L3 were 48.8% and 90.8%, respectively. When AFP-L3 was used in combination with PIVKA-II, 31 (46.3%) of the 67 patients with small less than 3 cm HCC were positive for at least one of these markers. CONCLUSION: PIVKA-II measured by sensitive EIA may be useful for the diagnosis of HCC with low AFP level. AFP-L3 and PIVKA-II may improve the detection rate of small HCCs less than 3 cm.
alpha-Fetoproteins ; Carcinoma, Hepatocellular* ; Diagnosis* ; Hepatitis, Chronic ; Humans ; Lens Plant ; Liver ; Liver Cirrhosis ; Liver Diseases ; Liver Neoplasms ; Prothrombin ; Sensitivity and Specificity ; Biomarkers, Tumor ; Vitamin K