Drug-induced cholestasis.

Acute, drug-induced hepatocellular cholestasis (either pure or cholestatic hepatitis) is a common manifestation of drug-induced hepatic injury. The drugs most frequently responsible are hormonal steroids and psychopharmacological agents (in particular phenothiazines and some antidepressants). Cholestasis usually subsides without sequelae in less than six months. Acute, drug-induced ductular cholestasis is uncommon and can resemble biliary tract obstruction. Complete recovery occurs promptly after the withdrawal of the causative drug in most cases. The pathogenetic mechanism may be immunoallergic. Prolonged ductular or ductal cholestasis can follow drug-induced acute hepatitis despite prompt withdrawal of the offending drug. This syndrome, observed mainly with chlorpromazine and uncommonly with twenty other drugs, is characterized by the progressive disappearance of small bile ducts and by manifestations mimicking primary biliary cirrhosis. However, its prognosis appears to be better than that of primary biliary cirrhosis, the condition being reversible in the majority of cases or even subsiding completely. The mechanism is still unknown, but several features suggest some form of autoimmunity. Extrahepatic cholestasis related to sclerosing cholangitis is a frequent and long-term complication of intra-arterial infusion of floxuridine in patients treated for hepatic metastases from colorectal carcinoma. Although it may be reversible, floxuridine-induced sclerosing cholangitis has a poor prognosis and can lead to death in a few patients. The mechanism is probably related to the vascular supply of the common hepatic duct and its relationship to the perfusion territory of floxuridine.