EARLY COLCHICINE ADMINISTRATION REDUCES HEPATIC-FIBROSIS AND PORTAL-HYPERTENSION IN RATS WITH BILE-DUCT LIGATION

Chronic administration of colchicine has been suggested as a potential treatment for hepatic fibrosis. The purpose of this study was to exam ine the effects of chronic oral administration of colchicine on the hi stological and hemodynamic abnormalities of bile duct ligation in the rat. Forty-eight rats with ligation-section of the common bile duct we re randomly and blindly assigned to receive either colchicine (50 mu/k g day) or placebo by gavage for 4 weeks. At the end of the treatment p eriod, morphometric analysis showed that hepatocyte and sinusoidal vol ume fractions were significantly higher in rats treated with colchicin e than in rats receiving placebo (42.4 +/- 1.3 vs. 32.1 +/- 2.6% (mean +/- S.E.) and 8.3 +/- 0.6 vs 4.7 +/- 0.4%, respectively), while bile duct volume fractions (reflecting bile ductular proliferation) and con nective tissue fractions were significantly lower in rats treated with colchicine than in rats receiving placebo (12.1 +/- 0.9 vs. 17.0 +/- 0.1% and 37.2 +/- 0.9 vs. 46.1 +/- 2.0%, respectively). Portal pressur e (13.4 +/- 0.7 vs. 17.8 +/- 0.5 mmHg), portal tributary blood flow (5 .8 +/- 0.4 vs. 8.7 +/- 0.5 ml.min-1.100 g-1) and cardiac index (40.8 /- 2.3 vs. 50.6 +/- 1.5 ml.min-1.100 g-1) were significantly lower in colchicine-treated rats than in placebo treated animals. In conclusion , in rats with bile duct ligation, colchicine limits the severity of l iver lesions and, consequently, of portal hypertension and hyperkineti c syndrome.