Hoekstra H Tian Y Jochum W Stieger B Graf R Porte RJ Clavien PA 2008 BACKGROUND Bile duct injury after hepatic artery thrombosis (HAT) in liver transplantation is believed to be caused by ischemia predominantly. We aimed to define the involvement of bile secretory dysfunction in the pathogenesis of liver injury after HAT. METHODS In a murine model, the main hepatic artery, the extrahepatic peribiliary plexus, or both arterial connections to the liver were interrupted (n=5 for each group). After 1, 14, or 28 days, hepatobiliary function was assessed by analysis of bile transporter expression, serum bile acids and bilirubin, and hepatic ATP content. In addition, cellular injury was assessed by light microscopy and biochemical markers. RESULTS There were no signs of hepatobiliary dysfunction or injury in sham-operated animals or in mice with interruption of the hepatic artery or the extrahepatic peribiliary plexus alone. However, as early as 24 hr after complete dearterialization, bile transporter expression was significantly reduced and intrahepatic cholestasis started to progress the following weeks. Histologic studies at 28 days after complete dearterialization showed severe hepatobiliary injury. CONCLUSIONS This study indicates that arterial blood supply is critical for normal bile secretion. Bile duct injury after complete arterial deprivation is preceded by a loss of bile secretory function and subsequent intrahepatic cholestasis. application/pdf https://sonar.ch/global/documents/4398 eng info:eu-repo/semantics/altIdentifier/doi/10.1097/TP.0b013e31816b2465 info:eu-repo/semantics/altIdentifier/pmid/18431237 info:eu-repo/semantics/openAccess Transplantation. - 2008 ATP Binding Cassette Transporter, Subfamily B ATP Binding Cassette Transporter, Subfamily B, Member 11 ATP-Binding Cassette Transporters Adenosine Triphosphate Animals Bile Biological Transport Cholestasis, Intrahepatic Cytokines Hepatic Artery Humans Ischemia Liver Mice Organic Anion Transporters, Sodium-Dependent RNA, Messenger Symporters Dearterialization of the liver causes intrahepatic cholestasis due to reduced bile transporter expression. http://purl.org/coar/resource_type/c_6501