Hépato-Gastro & Oncologie Digestive


Genetic cholestatic diseases Volume 22, issue 10, Décembre 2015


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Professeur honoraire à l’Université Paris 7,
1422, route des Mauvares,
13840 Rognes, France
* Tirés à part

Familial progressive intrahepatic cholestasis is a group of four diseases : type 1, due to a mutation of the ATP8B1 gene, encoding the protein FIC1 of the canalicular membrane of hepatocytes, type2, due to a mutation of the ABCB11 gene encoding the bile acid transporter BSEP, type 3, due to a mutation of the gene ABCB4, encoding the canalicular phospholipid floppase MDR3, and type 4, due to a mutation of the gene TJP2, encoding the tight junction protein TJP2. They are rare diseases (1 of 50,000 to 100,000 births), transmitted as autosomal recessive disorders. They present with pruritus and jaundice starting from the first months of life to adolescence or early adulthood. Cholestasis usually progresses to fibrosis and biliary cirrhosis, requiring a liver transplantation in about half of the cases at the average age of 7.5 years. The only medication capable of slowing the course of the disease and delaying or avoiding transplantation is ursodeoxycholic acid in type 3 patients. Benign recurrent cholestasis can be due to a mutation of ATP8B1 (type 1) or ABCB11 (type 2). It is also transmitted as an autosomal recessive disease. It manifests as episodes of severe pruritus and jaundice, recurring throughout life, and separated by asymptomatic intervals. It does not progress to fibrosis or cirrhosis. The treatment is purely symptomatic.