Review
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2017; 23(5): 763-775
Published online Feb 7, 2017. doi: 10.3748/wjg.v23.i5.763
Current and future therapies for inherited cholestatic liver diseases
Wendy L van der Woerd, Roderick HJ Houwen, Stan FJ van de Graaf
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
Wendy L van der Woerd, Roderick HJ Houwen, Department of Pediatric Gastroenterology, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, 3584 EA Utrecht, The Netherlands
Stan FJ van de Graaf, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, 1105 BK Amsterdam, The Netherlands
Author contributions: van der Woerd WL wrote the manuscript; van de Graaf SFJ created the figures; Houwen RHJ and van de Graaf SFJ reviewed and revised the manuscript; all authors read and approved the final version of the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wendy L van der Woerd, MD, PhD, Department of Pediatric Gastroenterology, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands. wwoerd@umcutrecht.nl
Telephone: +31-88-7555555 Fax: +31-88-7555312
Received: July 6, 2016
Peer-review started: July 9, 2016
First decision: September 12, 2016
Revised: November 16, 2016
Accepted: January 11, 2017
Article in press: January 11, 2017
Published online: February 7, 2017
Processing time: 199 Days and 16.2 Hours
Abstract

Familial intrahepatic cholestasis (FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. 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.

Keywords: Familial intrahepatic cholestasis; Progressive familial intrahepatic cholestasis; Inherited liver disease; ATP8B1; ABCB11; ABCB4; Biliary diversion; Mutation-targeted therapy; Personalized treatment

Core tip: Familial intrahepatic cholestasis (FIC) is a group of autosomal recessive liver diseases characterized by intrahepatic cholestasis. Phenotypes vary from only episodic disease to progressive FIC. Current therapeutic options are often insufficient to prevent progression of the disease. This review will discuss the current therapeutic regimen as well as the development of novel therapeutic strategies, focusing on surgical and pharmacological biliary diversion, hepatocyte transplantation and mutation-specific therapy.