REVERSIBILITY OF CHOLESTATIC CHANGES FOLLOWING EXPERIMENTAL COMMON BILE-DUCT OBSTRUCTION - FACT OR FANTASY

In 36 male Wistar rats extrahepatic cholestasis was induced by ligatio n and transsection of the common bile duct. After 1, 2 and 3 weeks of cholestasis the bile flow was restored by means of a Roux-en-Y choledo chojejunostomy. Plasma levels of bilirubin, alkaline phosphatase, GOT and clotting factor X were measured weekly. Liver biopsies were taken at the time of restored bile flow as well as 3 and 8 weeks thereafter. Histochemical reaction for lactate dehydrogenase activity and Sirius Red F3BA staining were used as measure for functional liver parenchyma and collagen, respectively. Acid phosphatase, alkaline phosphatase an d 5'-nucleotidase activities as well as the glycogen content were demo nstrated in cryostat sections of the same biopsies. After 1, 2 and 3 w eeks of common bile duct obstruction, levels of bilirubin, alkaline ph osphatase and GOT significantly increased, whereas levels of clotting factor X decreased. RBF resulted in normalization of all these levels to control range. The volume density of functional parenchyma was foun d to be reduced to 90%, 73% and 64% of the control values following 1, 2 and 3 weeks of common bile duct obstruction respectively, returning to 96%, 94% and 88% at 8 weeks, repectively, after restored bile flow . The collagen content increased significantly during cholestasis up t o 5-fold after 3 weeks of common bile duct obstruction. After restored bile flow, a slight decrease of collagen was measured in some animals but in none of the three groups a return to normal values appeared. C holestasis induced an alteration in localization and/or activity of th e three enzymes analyzed as well as a depletion of glycogen stores. Al l changes in activity and distribution pattern of the three enzymes, a s well as the glycogen depletion during common bile duct obstruction n ormalised after restored bile flow was performed. However, the longer common bile duct obstruction had existed, the longer period was needed for full recovery. In conclusion, even after 3 weeks of common bile d uct obstruction the parenchyma/stroma relationship grossly normalized after restored bile flow with an almost complete restoration of the pa renchyma and a concomitant recovery of liver function. However, collag en once formed, did not disappear but remained as more condensed septa , which apparently did not interfere with normal function.