Temporal Morphologic Changes in the Mouse Liver after Common Bile Duct Ligation

ABSTRACT

PURPOSE: Cholestasis is a common manifestation of biliary obstructive diseases. This study was designed to verify histopathologic manifestations of cholestatic liver injury after bile duct ligation in a murine model. METHODS: Eight-week-old female CB6 F1 mice underwent common bile duct ligation and sacrificed at various intervals after surgery. Serum samples were used for the levels of ALT, gamma-GT, total bilirubin. Liver tissues were used for H&E stain for histopathologic examination, Masson's trichrome to assess fibrosis, and reticulin for evaluation of hepatic lobular framework and cell loss. Data were analyzed using the Students' t-test. RESULTS: In mid-duct ligated animals, marked microvesicular fatty change was noted between 1 to 2 days, which completely subsided after 3 days. Scattered variable-sized foci of hepatic cell loss were noted also, beginning at 12 hours, but becoming more prominent at 1 to 3 days. Fibrosis in larger portal tracts near the hilum was first noted through day 3, and remained at days 7 and 28. This was accompanied by marked branching and/or epithelial proliferation in the large bile ducts. Peripheral hepatic fibrosis was evident at day 5 and continued postoperatively. Liver function tests on serums showed an obstructive jaundice pattern during the first week. These values normalized by week 4. Choledochoduodenal fistulae were formed in mice surviving 4 weeks after ligation. CONCLUSION: This study provides a temporally reproducible pattern of biochemical and histopathological changes in the liver, providing a useful model for studying the pathobiology of cholestatic liver diseases secondary to extrahepatic bile duct obstruction.