Plasma des‐γ‐carboxyprothrombin in the early stage of hepatocellular carcinoma

To evaluate the role of plasma des‐γ‐carboxyprothrombin in the early diagnosis of hepatocellular carcinoma, we simultaneously studied both des‐γ‐carboxyprothrombin activities by staphylocoagulase method and des‐γ‐carboxyprothrombin antigen levels by enzyme immunoassay in 39 patients with early stage hepatocellular carcinoma (tumor size <3 cm in 21 patients, 3 to 5 cm in 18 patients); 68 patients had large hepatocellular carcinoma and 54 patients had chronic hepatitis or cirrhosis. Des‐γ‐carboxyprothrombin levels by staphylocoagulase method (X) and enzyme immunoassay method (Y) on the same plasma specimens of hepatocellular carcinoma patients showed a linear correlation (Y = 0.15X ‐ 10.5, r = 0.533, n = 67, p < 0.001). Elevated des‐γ‐carboxyprothrombin activities were present in 10 of 21 patients (47.6%) with hepatocellular carcinoma <3 cm, 66.7% of 18 with hepatocellular carcinoma 3 to 5 cm, 67.6% of 68 with hepatocellular carcinomas >5 cm and 27.8% of 54 with chronic hepatitis or cirrhosis. The plasma des‐γ‐carboxyprothrombin levels did not correlate with the tumor size or serum α‐fetoprotein levels. Plasma des‐γ‐carboxyprothrombin and serum α‐fetoprotein measurements were comparable in the diagnosis of hepatocellular carcinoma because 22 (56.4%) and 21 (53.8%) of 39 patients with hepatocellular carcinoma <5 cm had increased des‐γ‐carboxyprothrombin and α‐fetoprotein levels, respectively. Up to 77% had an abnormal elevation in either marker. The des‐γ‐carboxyprothrombin antigen levels by enzyme immunoassay method are more specific to hepatocellular carcinoma than des‐γ‐carboxyprothrombin activities by the staphylocoagulase method: the positive rates of elevated des‐γ‐carboxyprothrombin antigen levels in the patients with hepatocellular carcinoma <3 cm, 3 to 5 cm, >5 cm and chronic hepatitis or cirrhosis were 19.0%, 55.6%, 66.2% and 14.8%, respectively. We conclude that des‐γ‐carboxyprothrombin assay may serve as a complementary tool in the diagnosis and follow‐up of hepatocellular carcinoma and is particularly useful in patients with normal or low α‐fetoprotein levels. Because of higher specificity to hepatocellular carcinoma and less tedious assay procedures, the enzyme immunoassay method is more practical than the staphylocoagulase method in the measurement of des‐γ‐carboxyprothrombin. For early detection of hepatocellular carcinoma, measurement of plasma des‐γ‐carboxyprothrombin levels only is not sensitive enough. (HEPATOLOGY 1990;11:481–488.)