BILIARY RETENTION IN A CHRONIC CHOLEDOCHO-VENOUS FISTULA IN THE RAT -INDUCTION OF PORTAL-HYPERTENSION BUT NOT OF BILIARY-CIRRHOSIS

In this study we investigated whether the retention of compounds which are excreted into the bile could contribute to portal hypertension in secondary biliary cirrhosis. Choledochovenous fistulas were grown in rats for 4 weeks. 6/13 of the animals had biochemical evidence of part ial obstruction. Microsomal function, as measured by the aminopyrine b reath test, was decreased in all animals with biliary retention while microsomal cytochrome P-450 content was decreased only in rats with ev idence of obstruction. All animals with biliary retention with or with out partial obstruction had portal hypertension. Animals with biliary retention and partial obstruction had hypercholeresis but decreased bi le salt excretion. All animals with a chronic catheter in the biliary tree had a loss of the negative permselectivity of the sinusoidal-cana licular barrier and decreased maximal bile secretory pressure. Only an imals with biochemical evidence of obstruction had moderate fibrosis a nd ductular proliferation as determined by stereological techniques. U nexpectedly, morphometric analysis also revealed an increase in hepato cyte mass induced by biliary retention. We conclude that bile contains a compound(s) which induces portal hypertension. This putative substa nce is neither bilirubin nor a bile acid since portal hypertension was also observed in animals with biliary retention without obstructive s igns.