Drug-induced cholestasis

• Drug-induced cholestasis may be due to impairment of hepatocellular bile secretion (pure cholestasis or cholestatic hepatitis), obstruction of ductules (cholangiolitis) or interlobular ducts (cholangitis), or extrahepatic obstruction (sclerosing cholangitis). • Mechanisms of hepatocellular cholestasis are multiple and include inhibition of various transport systems, cytoskeleton poisoning, disturbed intracellular calcium homeostasis and increased permeability with regurgitation of bile constituents into plasma. • Pure hepatocellular cholestasis is mostly observed with sex steroid hormones and anabolic steroids. • Ductular or ductal cholestasis (drug-induced cholangiopathy) may be acute and self-limited, or prolonged with ductopenia, occasionally leading to biliary cirrhosis. An immune mechanism has been proposed. • Sclerosing cholangitis with strictures near the confluent of hepatic ducts is observed after intraarterial administration of floxuridine for chemotherapy of hepatic metastases. • Some drugs may induce the formation of cholesterol gallstones, or precipitate in bile and form biliary sludge or stones in the gallbladder or common bile duct.