Pathophysiology of Cholestatic Liver Diseases: New Insights into the Mechanisms of Bile Infarct Formation

Abstract

Cholestatic liver diseases can be induced for many reasons including obstructions, e.g. by stones or tumors. An early consequence of obstructive cholestasis is the formation of bile infarcts, which refer to clusters of dead hepatocytes due to bile salt accumulation. Although these infarcts were described long time ago (in 1876 by Charcot and Gombault), the leading mechanism is still unclear. Some hypotheses suggested direct killing by accumulation of bile salts up to toxic levels. Others claim indirect cell death via immune cell infiltration and inflammatory cytokine release. However, the sequence of events leading to the formation bile infarcts are still unclear. In the recent issue of Hepatology, Ghallab and his colleagues have recorded in a time-resolved manner the key events leading to bile infarct formation and the subsequent systemic changes, using two-photon based intravital imaging. This mini-review highlights the results of this study and discuss the time-resolved events in acute and chronic cholestasis, as well as the link between biliary bile salts and hepatocyte death.

Keywords

• Cholestasis
• intravital imaging
• bile canaliculi
• bile salt toxicity
• bile leakage
• bile duct ligation.