New molecular aspects of cholestatic liver diseases

Hepatic uptake and biliary excretion of bile salts and non-bile salt organi c anions (e. g., bilirubin) is mediated by specific transport proteins loca ted at the basolateral and canalicular membranes of hepatocytes. Several he patobiliary transport systems have been identified and cloned over the past years. This development has facilitated molecular biological and genetic a nalyses of these transporters in experimental cholestasis and human cholest atic liver diseases. Evidence now exists that decreased or even absent expr ession of hepatobiliary transport systems may explain impaired transport fu nction resulting in hyperbilirubinemia and cholestasis. This review summari zes the molecular defects in hepatocellular membrane transporters associate d with hereditary and acquired forms of cholestatic liver diseases. The inc reasing information on the molecular regulation of hepatobiliary transport systems should bring new insights into the pathophysiology and treatment of human cholestatic liver diseases.