New perspectives for the treatment of cholestasis: Lessons from basic science applied clinically

The molecular basis of the bile formation and the adaptive responses that are known to occur in cholestatic liver injury is discussed. Current and possible future therapies for jaundice and cholestasis that are mediated by nuclear receptor ligands are also discussed. Cholestasis is a clinical syndrome that results from the disturbances in the formation of bile, a unique and vital property of liver. Steps in bile formation and metabolism can be divided into the four phases of hepatic uptake, hydroxylation, conjugation, and excretion. Adaptive responses are insufficient to prevent cholestasis from developing leading to up-regulation of several other transporters at the sinusoidal surface of the liver. Nuclear receptor medicine is being used to treat certain patients with cholestasis liver disease based on current knowledge of the diverse effects of nuclear receptor ligands and activators on bile acid metabolism and bile acid transporters.