Novel insight into mechanisms of cholestatic liver injury Journal Article

Authors: Woolbright Benjamin L; Jaeschke, Hartmut
Article Title: Novel insight into mechanisms of cholestatic liver injury
Abstract: Cholestasis results in a buildup of bile acids in serum and in hepatocytes. Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acid-induced apoptosis as the major cause of hepatocellular injury. Recent work has focused both on the role of bile acids in cell signaling as well as the role of sterile inflammation in the pathophysiology. Advances in modern analytical methodology have allowed for more accurate measuring of bile acid concentrations in serum, liver, and bile to very low levels of detection. Interestingly, toxic bile acid levels are seemingly far lower than previously hypothesized. The initial hypothesis has been based largely upon the exposure of mumol/L concentrations of toxic bile acids and bile salts to primary hepatocytes in cell culture, the possibility that in vivo bile acid concentrations may be far lower than the observed in vitro toxicity has far reaching implications in the mechanism of injury. This review will focus on both how different bile acids and different bile acid concentrations can affect hepatocytes during cholestasis, and additionally provide insight into how these data support recent hypotheses that cholestatic liver injury may not occur through direct bile acid-induced apoptosis, but may involve largely inflammatory cell-mediated liver cell necrosis.
Journal Title: World journal of gastroenterology : WJG
Volume: 18
Issue: 36
ISSN: 1007-9327
Publisher: WJG Press  
Publication Place: China
Date Published: 2012-09-28
Start Page: 4985
End Page: 93
Language: eng
Identifier: 23049206
Notes: In-Process
KUMC Authors
  1. Hartmut Jaeschke
    256 Jaeschke
Related KUMC Work