Elevated serum aminoterminal procollagen type-III-peptide parallels collagen accumulation in rats with secondary biliary fibrosis.
OBJECTIVE
The aminoterminal procollagen type-III-peptide, which can be released during collagen type III deposition, has been suggested as a serum marker of fibrogenesis in patients with chronic liver disease. However, longitudinal studies correlating procollagen type-III-peptide concentrations in serum with the evolution of liver fibrosis are still needed. The purpose of the present study was to prove the significance of procollagen type-III-peptide concentrations in serum as a non-invasive marker of liver fibrogenesis in an animal model that best resembles progressive human liver fibrosis.


METHODS
In 88 female Wistar rats the biliary system was occluded by double ligation of the choledochal duct followed by retrograde injection of a mixture of prolamine/ethanole (Ethibloc). Sixteen rats served as controls. Groups of 8-10 rats were sacrificed at days 2, 7, 14, 21, 30, 32, 35, 60 and 90 after bile duct occlusion. In the groups histological staging (fibrosis score), determination of total liver hydroxyproline, measurement of serum procollagen type-III-peptide and routine liver function tests were performed.


RESULTS
First histological signs of liver fibrosis were seen as early as 7 days after bile duct occlusion. Progressive fibrosis was paralleled by an increase of serum procollagen type-III-peptide. There was a significant correlation between serum procollagen type-III-peptide and histological stages of fibrosis (r = 0.80; p < 0.0001) as well as between serum procollagen type-III-peptide and hydroxyproline in total liver tissue (r = 0.85; p < 0.0001)


CONCLUSIONS
These results indicate that: (1) complete bile duct occlusion in rats produces progressive hepatic fibrosis resembling human secondary biliary fibrosis, and (2) procollagen type-III-peptide concentrations in serum reflect ongoing collagen formation in the liver unrelated to serum markers of cholestasis and inflammation.
Gerling
B
B
Department of Pediatrics, KAVH, Virchow-Klinikum, Humboldt University of Berlin, Germany.
Becker
M
M
Waldschmidt
J
J
Rehmann
M
M
Schuppan
D
D
D000818:Animals; D002779:Cholestasis / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D008106:Liver Cirrhosis, Experimental / Q000097:blood* / Q000209:etiology; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar
D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D006909:Hydroxyproline