Abstract
Glycylprolyl dipeptidyl aminopeptidase (GP-DAP) activity was measured in 333 healthy subjects and 270 patients with various hepatobiliary diseases by the method of Nagatsu et al. The level in the serum of healthy subjects (age, 20-82 years) was 75.1±13.4 mU/ml (mean±SD). It decreased with age in the male subjects, while it increased in the female subjects aged more than 50 years.
The levels in patients with acute hepatitis (123.4±33.4), chronic hepatitis (107.6±31.7), cirrhosis (98.9±38.5), hepatocellular carcinoma (HCC) (124.6±49.0) and extrahepatic obstructive jaundice (139.7±57.3) were significantly higher compared with the healthy subjects, respectively (p<0.01). The level in acute hepatitis was significantly higher than that found in chronic hepatitis (p<0.01) and cirrhosis (p<0.01), respectively. The level in HCC was significantly higher than that in cirrhosis (p<0.01). There was a significant positive correlation between GP-DAP and biliary tract enzymes, including alkaline phosphatase, leucine aminopeptidase and γ-glutamyl transpeptidase, in acute hepatitis, chronic hepatitis and cirrhosis, respectively, while in HCC no relation was found between them. Moreover, though there was a positive correlation between GP-DAP and serum γ-globulin in chronic hepatitis, there was a negative correlation between them in HCC, suggesting some different mechanisms in the increase of serum GP-DAP in HCC from the other three diseases.
In HCC, though serum GP-DAP did not correlate with serum α-fetoprotein, it tended to increase with the size of the tumor on imaging diagnosis, including angiography and computed tomography. Gradual increase was observed in cases of cirrhosis which developed into HCC. In autopsied cases of HCC, the concentration of GP-DAP in the cancer tissues (45.52±26.75 mU/mg protein, n=8) was significantly higher than in the noncancerous cirrhotic portions (14.38±6.30, n=9, p<0.05) of identical materials, and in liver tissue with non-hepatic diseases (8.90±3.22, n=14, p<0.01). A positive correlation was found between the activity of GP-DAP in serum shortly before death and in cancer tissue, suggesting that GP-DAP was being released from the epatoma tissue into the serum.
