title: Current and future therapies for inherited cholestatic liver diseases.
abstract: Familial intrahepatic cholestasis (FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations inATP8B1,ABCB11andABCB4. Phenotypes range from benign recurrent intrahepatic cholestasis (BRIC), associated with recurrent cholestatic attacks, to progressive FIC (PFIC). Patients often suffer from severe pruritus and eventually progressive cholestasis results in liver failure. Currently, first-line treatment includes ursodeoxycholic acid in patients with ABCB4 deficiency (PFIC3) and partial biliary diversion in patients with ATP8B1 or ABCB11 deficiency (PFIC1 and PFIC2). When treatment fails, liver transplantation is needed which is associated with complications like rejection, post-transplant hepatic steatosis and recurrence of disease. Therefore, the need for more and better therapies for this group of chronic diseases remains. Here, we discuss new symptomatic treatment options like total biliary diversion, pharmacological diversion of bile acids and hepatocyte transplantation. Furthermore, we focus on emerging mutation-targeted therapeutic strategies, providing an outlook for future personalized treatment for inherited cholestatic liver diseases.
authors.affiliation: Wendy L van der Woerd, Stan FJ van de Graaf, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: van der Woerd
authors.affiliation: Wendy L van der Woerd, Stan FJ van de Graaf, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Roderick Hj
authors.initials: RH
authors.lastname: Houwen
authors.affiliation: Wendy L van der Woerd, Stan FJ van de Graaf, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Stan Fj
authors.initials: SF
authors.lastname: van de Graaf
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D001647:Bile Acids and Salts / Q000378:metabolism; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000601:surgery / Q000628:therapy*; D006801:Humans; D016031:Liver Transplantation; D058990:Molecular Targeted Therapy; D009154:Mutation; D057285:Precision Medicine
chemical_list: C093491:ABCB11 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; C095122:multidrug resistance protein 3; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human
keywords: ABCB11; ABCB4; ATP8B1; Biliary diversion; Familial intrahepatic cholestasis; Inherited liver disease; Mutation-targeted therapy; Personalized treatment; Progressive familial intrahepatic cholestasis