Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-5849
Hoekstra, H; Tian, Y; Jochum, W; Stieger, B; Graf, R; Porte, R J; Clavien, P A (2008). Dearterialization of the liver causes intrahepatic cholestasis due to reduced bile transporter expression. Transplantation, 85(8):1159-1166.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology|
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
|DDC:||610 Medicine & health|
|Deposited On:||25 Nov 2008 11:54|
|Last Modified:||27 Nov 2013 17:55|
|Publisher:||Lippincott Wiliams & Wilkins|
|Citations:||Web of Science®. Times cited: 6|
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