AMINOTERMINAL PROPEPTIDE OF TYPE-III PROCOLLAGEN - A MARKER OF HEPATIC-FIBROSIS AFTER BILE-DUCT OBSTRUCTION IN THE MONKEY

Background/Aims: In an experimental study in monkeys, liver fibrosis d evelopment after segmental bile duct obstruction was investigated and correlated with the aminoterminal propeptide of type procollagen (PIII NP). Materials and Methods: Segmental bile duct obstruction. was produ ced by ligation and section, of the left hepatic bile duct in all monk eys. Fibrosis induction was examined by intravenous leukotriene C4 (LT C4,5nmol/kg) application, endogenous LT-production stimulated by endot oxin (LPS,salmonella abortus equi, 50 ng/kg), fibrosis inhibition. by dexamethasone (1 mg/kg) intramuscularly and subsequent endogenous LT-p roduction, 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 specif ic radioimmunoassay each week and correlated with the morphometric res ults. Results: Bile duct obstruction. leads to secondary sclerosing ch olangitis with bile duct vanishing and subsequent biliary cirrhosis co mbined with perivenous sclerosis and cavernous transformation of the t erminal 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 fro m 1.05+/-0.03% up to: controls 6.1+/-0.9%, dexamethasone 5.9+/-0.8%, L PS 8.2+/-0.8%, LTC4 9.075+/-1.4%. PIIINP concentration rose within 6 w eeks in, the controls with hepatic bile duct obstruction fi om 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/m l. After 12 weeks, PIIINP decreased in the controls resp. after dexame thasone to 41.25+/-6.94 ng/ml resp. 33.5+/-7.72 ng/ml and increased af ter 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 . Conclusion: PIIINP determination, after segmental bile duct obstruct ion correlates with collagen deposition and allows evaluation of hepat ic fibrosis activity.