Reversibility of cholestatic changes following experimental common bile duct obstruction: fact or fantasy?

Abstract

In 36 male Wistar rats extrahepatic cholestasis was induced by ligation 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 choledochojejunostomy. 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 and 5'-nucleotidase activities as well as the glycogen content were demonstrated in cryostat sections of the same biopsies. After 1, 2 and 3 weeks of common bile duct obstruction, levels of bilirubin, alkaline phosphatase 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 found 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, respectively, after restored bile flow. The collagen content increased significantly during cholestasis up to 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. Cholestasis induced an alteration in localization and/or activity of the three enzymes analyzed as well as a depletion of glycogen stores. All changes in activity and distribution pattern of the three enzymes, as well as the glycogen depletion during common bile duct obstruction normalised 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 duct obstruction the parenchyma/stroma relationship grossly normalized after restored bile flow with an almost complete restoration of the parenchyma and a concomitant recovery of liver function. However, collagen once formed, did not disappear but remained as more condensed septa, which apparently did not interfere with normal function.