Aminoterminal propeptide of type III procollagen: a marker of hepatic fibrosis after bile duct obstruction in the monkey.
OBJECTIVE
In an experimental study in monkeys, liver fibrosis development after segmental bile duct obstruction was investigated and correlated with the aminoterminal propeptide of type III procollagen (PIIINP).


METHODS
Segmental bile duct obstruction was produced by ligation and section of the left hepatic bile duct in all monkeys. Fibrosis induction was examined by intravenous leukotriene C4 (LTC4, 5 nmol/kg) application, endogenous LT-production stimulated by endotoxin (LPS,salmonella abortus equi, 50 ng/kg), fibrosis inhibition by dexamethasone (1 mg/kg) intramuscularly and subsequent endogenous LT-production stimulation by LPS (50 ng/kg). Ligated and unligated liver lobe biopsies were taken 3, 7 and 12 weeks after ligation. All portal areas were measured morphometrically. PIIINP was measured by a specific radioimmunoassay each week and correlated with the morphometric results.


RESULTS
Bile duct obstruction leads to secondary sclerosing cholangitis with bile duct vanishing and subsequent biliary cirrhosis combined with perivenous sclerosis and cavernous transformation of the terminal vein. The collagen concentration increased in the nonligated lobe from mean +/-SEM 1.05 +/- 0.03% to 1.53 +/- 0.19% only after LTC4 and with no difference in the other groups. In the ligated lobe collagen concentration increased significantly in all groups continuously from 1.05 +/- 0.03% up to: controls 6.1 +/- 0.9%, dexamethasone 5.9 +/- 0.8%, LPS 8.2 +/- 0.8%, LTC4 9.075 +/- 1.4%. PIIINP concentration rose within 6 weeks in the controls with hepatic bile duct obstruction from 34.43 +/- 15 ng/ml up to 57 +/- 13.27 ng/ml, after dexamethasone to 48.5 +/- 18.23 ng/ml, after LPS to 57 +/- 13.27 ng/ml, after LTC4 to 80.25 +/- 16.04 ng/ml. After 12 weeks, PIIINP decreased in the controls resp. after dexamethasone to 41.25 +/- 6.94 ng/ml resp. 33.5 +/- 7.72 ng/ml and increased after LPS resp. LTC4 up to 64.25 +/- 17.07 ng/ml resp.104 +/- 22.46 ng/ ml. The correlation of collagen deposition and PIIINP was in the controls r = 0.83, after dexamethasone r = 0.71, after LPS r = 0.83 after LTC4 r = 0.91.


CONCLUSIONS
PIIINP determination after segmental bile duct obstruction correlates with collagen deposition and allows evaluation of hepatic fibrosis activity.
Ruf
G
G
Department of General Surgery, University of Freiburg, Germany.
Mappes
H J
HJ
Koch
H
H
Baumgartner
U
U
Hagmann
W
W
Farthmann
E H
EH
D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002779:Cholestasis / Q000150:complications*; D003094:Collagen / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D017997:Leukotriene C4 / Q000494:pharmacology; D008099:Liver / Q000737:chemistry; D008106:Liver Cirrhosis, Experimental / Q000175:diagnosis*; D008252:Macaca fascicularis; D010446:Peptide Fragments / Q000032:analysis*; D011347:Procollagen / Q000032:analysis*; D011863:Radioimmunoassay
D015415:Biomarkers; D004731:Endotoxins; D005938:Glucocorticoids; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D017997:Leukotriene C4; D003907:Dexamethasone; D003094:Collagen