RELATIONSHIP BETWEEN SERUM AND HEPATIC 7S FRAGMENTS OF TYPE-IV COLLAGEN IN CHRONIC LIVER-DISEASE

We evaluated the mechanism of increased serum concentrations of the 7S fragment of the N-terminal domain of type IV collagen (7S collagen) i n chronic Liver disease, We measured the concentrations of hepatic-fre e and deposited 7S collagens after extraction with Tris-HCl buffer and bacterial collagenase, then compared them with the serum levels in 8 normal controls and 48 patients with chronic liver disease. The hepati c 7S collagen levels extracted with Tris-HCl buffer and collagenase ac counted for 7% and 93%, respectively, of the total 7S collagen levels in normal controls. Both hepatic 7S collagen levels as well as serum l evels increased in accordance with the progress of Liver disease. Seru m levels of 7S collagen showed a closer correlation with the hepatic 7 S collagen levels extracted with Tris-HCl buffer (r = .822), compared with those extracted with collagenase (r = .382). On the other hand, t he histological degrees of liver fibrosis were highly correlated with the hepatic collagenase-extracted 7S collagen levels (r = .822), compa red with serum and the hepatic Tris-HCl buffer-extracted levels (r = . 478 and r = .537, respectively), Although there was no difference in s erum and hepatic 7S collagen levels between B and C viral patients, th e serum and hepatic Tris-HCl buffer-extracted 7S collagen levels were higher in patients with alcoholic cirrhosis than patients with viral c irrhosis. However, the hepatic collagenase-extracted levels were simil ar in both groups. Gel filtration demonstrated that the serum and hepa tic Tris-HCl buffer-extracted 7S collagens were mainly eluted in the m acromolecular 7S collagen-reactive fraction in cirrhosis, whereas the hepatic collagenase-extracted 7S collagen was eluted in the authentic 7S collagen-reactive fraction, The results suggest that serum 7S colla gen levels are not a particularly reliable measure of hepatic fibrosis but reflect the enhanced metabolism, especially synthesis of type IV collagen in the liver.