Collagen proline hydroxylase activity and 35S sulphate uptake in human liver biopsies

Abstract

In an effort to assess connective tissue biosynthetic activity in human liver disease, collagen proline hydroxylase (a key enzyme in collagen biosynthesis) and the uptake of ³⁵S sulphate (a precursor of sulphated mucopolysaccharides) were measured in hepatic tissue obtained mainly by percutaneous biopsy. A procedure is described for the quantitation of collagen proline hydroxylase in cryostat sections which allows for the simultaneous histopathological examination of the liver specimen. A three to eightfold increase in the activity of this enzyme was found in four cirrhotic livers compared with the mean value of four normal livers and two biopsies from patients with Gilbert's syndrome. Elevated hydroxylase levels were found also in five patients with hepatic dysfunction but without cirrhosis (four alcoholics and one patient with persistent hepatitis associated with serum smooth muscle antibody). It is suggested that the hepatic level of collagen proline hydroxylase may be a useful quantitative index of fibroblastic activity in human liver disease. Autoradiographic studies of radioactive sulphate uptake in biopsy specimens from patients with chronic liver disease showed an exaggerated incorporation of isotope not only at sites of established fibrogenesis but also in the walls of sinusoids throughout the liver.