Cell Death and microRNAs in Cholestatic Liver Diseases: Update on Potential Therapeutic Applications

Cholestasis is the main pathogenic event in a wide range of genetic or acquired disorders of bile acid synthesis or bile flow, resulting in intrahepatic and systemic accumulation of bile acids. In turn, augmented levels of bile acids lead to hepatocellular injury and progressive liver damage, eventually culminating in fibrosis and end-stage liver disease. In the injured cholestatic liver, apoptosis has long been recognized as a direct consequence of bile acid-mediated injury. It is now apparent that inflammation and necrosis play an equal or even more prevalent role. Ursodeoxycholic acid is the mainstream treatment for several cholestatic syndromes, but has limited efficacy in certain circumstances. With the notion that miRNAs play key roles in basic biological processes and that their deregulation is common in human liver disease, prospective use of miRNAs as either therapeutic targets or disease biomarkers is now being increasingly documented. Deciphering the exact contribution of each player is crucial for directing efforts toward finding much needed novel therapeutic strategies for cholestasis.