Drug- And Chemical-Induced Cholestasis

Cholestasis resulting from medicinal and chemical agents is an increasingly well-recognized cause of liver disease. Although the consequences of cholestatic injury are generally regarded as being far less serious than those of acute parenchymal injury with a risk of fulminant hepatitis, the significance of drug-induced cholestasis is revealed by the broad spectrum of acute and chronic clinical syndromes producing jaundice and bile duct injury that can mimic extrahepatic biliary obstruction, primary biliary cirrhosis, and sclerosing cholangitis. In the more than 10 years since the authors last reviewed drug-induced cholestasis,153 several agents have been added to the list of cholestatic hepatotoxins, and significant advances have been made in the understanding of the pathophysiology of cholestasis. This article reviews the various forms of drug-induced cholestasis, focusing on the clinicopathologic features of this form of hepatic injury and on the known or putative mechanisms by which drugs and chemicals lead to cholestasis. Current concepts concerning the pathogenesis and molecular biology of cholestasis have been recently reviewed by others133 and will not be included here.