Vanishing bile duct syndrome in drug-induced liver disease

Abstract

T HE TERM bile duct syndromes refers to a series of cholestatic liver diseases characterized by progressive destruction of segments of the intrahepatic biliary tree (1). One of the possible aetiologies is drug-induced, toxic bile duct damage. This category of drug-induced and toxic liver injuries is subject to the following general considerations. • Drug-induced liver damage associated with lesions and destruction of intrahepatic bile ducts presumably affects both hepatocytes and bile duct cells, since the acute phase is characterized by parenchymal bilirubinostasis and a hepatitic component with increased aminotransferases (2) in association with portal inflammatory lesions including destructive cholangitis of interlobular bile ducts (3). • Although bile duct epithelial cells have the capacity to multiply and to regenerate under the influence of appropriate stimuli (4), it appears that bile ducts, as complete epithelium-lined tubes, are only rarely reconstructed once they have been completely destroyed and replaced by connective tissue scars (5). It comes as no surprise then that drug-induced liver disease associated with disappearance of intrahepatic bile ducts results in long-lasting, chronic cholestasis. • Understandably, drug-induced cholestatic liver disease associated with disappearance of intrahepatic bile ducts resembles other vanishing bile duct disorders,' both clinically and histologically. This explains why several reports in the past compared this drug-induced pathological state with naturally occurring diseases like Primary Biliary Cirrhosis (PBC) (6). In some instances, drugs have even been suggested to be the cause of PBC. It seems more probable, however, that some cases represent a co-