New molecular features of cholestatic diseases of the liver

Hepatic uptake and biliary excretion of bile salts and non-bile salt organic anions is mediated by specific transport proteins located at the basolateral and canalicular membranes of hepatocytes. Several hepatobiliary transport systems have been identified and cloned over the past years. This development has facilitated molecular biological and genetic analyses of these transporters in experimental cholestasis and human cholestatic liver diseases. Evidence now exists that decreased or even absent expression of hepatobiliary transport systems may explain impaired transport function resulting in hyperbilirubinemia and cholestasis. This review summarizes the molecular defects in hepatocellular membrane transporters associated with hereditary and acquired forms of cholestatic liver diseases. The increasing information on the molecular regulation of hepatobiliary transport systems should bring new insights into the pathophysiology and treatment of human cholestatic liver diseases.