John Libbey Eurotext

Hépato-Gastro & Oncologie Digestive


Pathophysiology of cholestasis Volume 19, issue 1, Janvier 2012


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Université Paris 7, 1422 route des Mauvares, 13840 Rognes
  • Key words: bile secretion, bile flow, hepatocytes, cholangiocytes, bile acids and salts, bilirubin, phospholipids
  • DOI : 10.1684/hpg.2012.0678
  • Page(s) : 14-20
  • Published in: 2012

Cholestasis is a decrease or a cessation of bile flow. Cholestasis can be due to an alteration of bile secretion by hepatocytes, as in progressive familial intrahepatic cholestasis, benign recurrent cholestasis or cholestasis of pregnancy, or to alterations of bile ductules or ducts resulting in biliary obstruction, as in cystic fibrosis, primary biliary cirrhosis or primary sclerosing cholangitis. Here, we review the molecular mechanisms leading to cholestasis, in particular the mutations of carriers on hepatocytes or cholangiocytes. Mutations of the canalicular transporter of phosphatidyl choline, MDR3, cause type 3 progressive familial intrahepatic cholestasis, as well as some forms of cholestasis of pregnancy with high y-GT and a peculiar form of intrahepatic cholesterol cholelithiasis, known as the low phospholipid-associated cholestasis and cholelithiasis syndrome. Similarly, mutations of an aminophospholipid carrier, FIC1, or of the canalicular bile acid transporter BSEP lead to other phenotypes of progressive familial intrahepatic cholestasis, respectively types 1 and 2. Cholestasis associated with cystic fibrosis is due to mutations of the cholangiocyte chloride channel CFTR. The molecular mechanisms of the lesions of primary biliary cirrosis and primary sclerosing cholangitis are still unknown. These molecular advances in the understanding of cholestasis potentially open the way to targeted therapies of cholestatic syndromes.