P105 Biliary drainage in a rat: a long-term continuous drainage model resulting in liver damage and an altered FXR pathway, lipid and cholesterol metabolism

IntroductionWe hypothesised that the development of intestinal failure associated liver disease (IFALD) caused by an enterocutaneous fistula in which the enterohepatic circulation is interrupted without obstructive cholestasis leads to reduced farnosoid X receptor (FXR) signalling, ultimately leading to liver damage. Previous studies have primarily been performed in models of bile duct obstruction.AimTherefore we aimed to develop a biliary diversion model in the rat with long-term continuous biliary drainage and determined its effect on hepatic function and lipid metabolism.MethodsIn rats (n=7–9), the bile duct was cannulated and externalised to accomplish biliary drainage. Sham controls underwent laparotomy without cannulation. Rats were sacrificed after 3 and 7 days, and liver samples were collected for histological assessment (necrosis, inflammation, bile duct proliferation). Sirius red staining and Oil Red O staining were used for analysis of fibrosis and steatosis, respectively. Quantitative PCR was performed for genes involved in the FXR pathway (FXR, SHP, BSEP, CYP7A1 and CYP8B1), lipid and cholesterol metabolism (FAS, SREBF, ACACA, PPARg, SCD1, LDLr and HMG-CoA reductase). AST, ALT, AP, GGT and bilirubin (total and direct) were assessed.ResultsContinuous biliary diversion resulted in increased hepatic inflammation and necrosis at day 3 and day 7 (p