Ductular proliferation and hepatic secretory function in experimental fascioliasis

Proliferation of bile duct-like epithelial cells is a common feature of extrahepatic biliary obstruction and it is also present in other forms of liver disease. Experimental infestation with Fasciola hepatica induces hyperplasia of ductular cells together with different functional alterations, such as hypercholeresis, in the rat. We have investigated the contribution of ductular biliary secretion to the hypercholeretic phenomenon in rats with experimental fascioliasis. Infestation was induced by oral administration of 20 metacercariae of F. hepatica. Twelve weeks later, histological study of the liver showed a hyperplastic reaction with proliferation of bile duct-like structures. Basal bile flow in infested animals was significantly higher than that of control animals (+17%), while biliary secretion of bile acids did not significantly differ between both groups. Bile flow increase was associated in parasitized animals with a significantly lower [14C]mannitol bile:plasma ratio (-23%). Intravenous secretin administration (0.3 CU/100 g body wt min) induced a significant increase in the biliary concentration of bicarbonate (+21%) and an enhancement of bile flow (+21%) only in the animals with ductular proliferation. Taurocholate infusion (0.5 nmol/100 g body wt min) produced a similar bile flow increase both in control rats and in rats with proliferated biliary ductules. These results indicate that proliferated bile ductules and ducts spontaneously secrete bile in response to infestation by F. hepatica and that secretin-stimulated bile flow originates at the proliferated biliary structures.