Sensitive measurement of serum abnormal prothrombin (PIVKA-II) as a marker of hepatocellular carcinoma

BACKGROUND/AIMS: The usefulness of abnormal prothrombin (PIVKA-II) for diagnosis of small HCC has been limited by its low sensitivity, despite a high specificity. METHODOLOGY: The serum concentration of PIVKA-II was determined by using a new sensitive enzyme immunoassay (EIA) kit in patients with hepatocellular carcinoma (I-ICC), liver cirrhosis (LC), or chronic hepatitis(CH) and normal controls (NC). alpha-Fetoprotein (AFP) was simultaneously determined in same patients. RESULTS: This kit has made it possible to detect low concentrations of PIVKA-II in the NC. The serum PIVKA-II concentration (mean +/-SE) was 15.7+/-1.1mAu/ml, 16.1+2.0mAu/ml, 26.3+/-7.2mAu/ml and 5420.3+/-3960.0mAu/ml in NC, CH, LC and HCC, respectively. Among 106 patients with HCC, 74 patients (69.8%) were positive for PIVKA-II (greater than or equal to 40mAu/ml), while only 9 patients out of 68 patients with LC were positive (13.2%) and only 2 out of 90 patients with CH were positive (2.2%). No significant correlation was observed between AFP and PIVKA-II levels. With combined assay of AFP and PIVKA-II, the positive rate for HCC was increased to 78.3%. Among 14 patients with HCC <20mm in diameter, 7 were positive for PIVKA-II, and 6 out of 10 patients with HCC between 20 and 30mm in diameter were positive for PIVKA-II. There was a correlation between tumor size and the PIVKA-II level. CONCLUSIONS: Determination of PIVKA-II by this new EIA kit could be useful for the diagnosis of HCC, especially combined with determination of AFP.