We evaluated the mechanism of increased serum concentrations of the 7S fragment of the N-terminal domain of
type IV collagen (
7S collagen) in chronic
liver disease. We measured the concentrations of hepatic-free 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 hepatic
7S collagen levels extracted with Tris-HCl
buffer and
collagenase accounted for 7% and 93%, respectively, of the total
7S collagen levels in normal controls. Both hepatic
7S collagen levels as well as serum levels increased in accordance with the progress of
liver disease. Serum levels of
7S collagen showed a closer correlation with the hepatic
7S collagen levels extracted with Tris-HCl
buffer (r = .822), compared with those extracted with
collagenase (r = .382). On the other hand, the histological degrees of
liver fibrosis were highly correlated with the hepatic
collagenase-extracted
7S collagen levels (r = .822), compared with serum and the hepatic Tris-HCl
buffer-extracted levels (
r = .478 and r = .537, respectively). Although there was no difference in serum and hepatic
7S collagen levels between B and C viral patients, the serum and hepatic Tris-HCl
buffer-extracted
7S collagen levels were higher in patients with
alcoholic cirrhosis than patients with viral
cirrhosis. However, the hepatic
collagenase-extracted levels were similar in both groups. Gel filtration demonstrated that the serum and hepatic Tris-HCl
buffer-extracted 7S
collagens were mainly eluted in the macromolecular
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 collagen levels are not a particularly reliable measure of hepatic
fibrosis but reflect the enhanced metabolism, especially synthesis of
type IV collagen in the liver.