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.