To evaluate the diagnostic significance of the collagen Type I11 (Col 1-3) N-terminal propeptide of procollagen Type 111, with respect to activity and degree of liver fibrosis, Col 1-3 serum concentrations were measured in 11 1 patients with chronic liver diseases and in 60 patients were correlated with liver histology and morphometry. Col 1-3 was measured by a specific radioimmunoassay. Biopsies were read without knowledge of diagnosis. Periportal and intralobular lesions were assessed semiquantitatively by allocating 1 of 4 severity grades to each parameter. All portal areas were measured morphometrically. Compared to 27 normal controls, Col 1-3 concentrations were significantly elevated in patients with untreated chronic active hepatitis, cirrhosis and primary biliary cirrhosis, but not in chronic persistent hepatitis or fatty liver. Morphometrically measured portal tract area significantly correlated with Col 1-3 plasma levels. Among the semiquantitatively measured periportal lesions, the number of fibroblasts exhibited the closest relationship with Col 1-3 levels; there was no relationship between Col 1-3 levels and intralobular lesions. These data suggest that Col 1-3 serum levels reliably reflect the activity and degree of liver fibrosis and are useful along with liver biopsy in follow-up of patients with chronic liver disease.
Noninvasive assessment of hepatocyte functions, cell necrosis and inflammation are well established; however, the number of connective tissue cells and the extent of collagen can only be estimated by liver biopsy which does not provide a dynamic picture of fibrogenesis and is limited by sampling error. Since fibrosis frequently determines the course and prognosis of chronic liver disease, a noninvasive test for assessment of liver fibrosis would be very helpful in management of chronic hepatic disease.
Hepatic fibrosis is characterized by increased synthesis and deposition of collagen in the interstitial space. Enzymes involved in posttranslational modification of liver procollagen have been measured in experimental and human liver disease, and their activities have been related to the rate of collagen synthesis (1). Although correlation between hepatic prolylhydroxylase activity