Cholestatic syndromes

Abstract

In this chapter recent advances in the understanding and treatment of a number of cholestatic syndromes are discussed. Therapeutically, current evidence suggests that the hydrophilic bile acid ursodeoxycholic acid is useful in the treatment of a number of cholestatic conditions, including primary biliary cirrhosis, cholestasis of pregnancy, and the liver disease associated with cystic fibrosis. New insights into the etiology of conditions such as primary sclerosing cholangitis (PSC) and some forms of hereditary cholestasis have recently been identified. It has been suggested that PSC may be linked to ischemic damage to bile ducts, secondary to the hypercoagulable state that can accompany PSC, or to the release of fibrinogenic cytokines by mast cells infiltrating the biliary epithelium. Furthermore, a number of studies have suggested that a link exists between concurrent ulcerative colitis and an increased incidence of cholangiocarcinoma and colonic neoplasia in patients with PSC and ulcerative colitis. Moreover, smoking may be protective with respect to the development of PSC in patients with ulcerative colitis. Defects in multidrug resistance gene products have been identified in some forms of hereditary cholestasis, including progressive familial intrahepatic cholestasis and Dubin-Johnson syndrome. Finally, the etiology of cholestatic liver test abnormalities have been examined in a number of conditions characterized by immunosuppression; bone marrow transplanation, HIV, and hepatitis C in the setting of liver transplantation. A rapidly progressive, severe form of fibrosing cholestasis has been documented in a minority of patients undergoing liver transplantation for hepatitis C.