Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2020; 26(47): 7470-7484
Published online Dec 21, 2020. doi: 10.3748/wjg.v26.i47.7470
Molecular overview of progressive familial intrahepatic cholestasis
Sriram Amirneni, Nils Haep, Mohammad A Gad, Alejandro Soto-Gutierrez, James E Squires, Rodrigo M Florentino
Sriram Amirneni, Nils Haep, Mohammad A Gad, Alejandro Soto-Gutierrez, Rodrigo M Florentino, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, United States
Alejandro Soto-Gutierrez, James E Squires, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, United States
James E Squires, Division of Gastroenterology, Hepatology, and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States
Author contributions: All authors contributed to this paper with literature review and analysis and approval of the final version.
Supported by NIH, No. UG3TR003289 to Soto-Gutierrez A.
Conflict-of-interest statement: A.S.-G., is co-founder and have a financial interest in Von Baer Wolff, Inc. a company focused on biofabrication of autologous human hepatocytes from stem cells technology and programming liver failure and their interests are managed by the Conflict of Interest Office at the University of Pittsburgh in accordance with their policies
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Rodrigo M Florentino, PhD, Research Fellow, Department of Pathology, University of Pittsburgh, 200 Lothrop Street S420 Biomedical Science Tower, Pittsburgh, PA 15213, United States.
Received: September 11, 2020
Peer-review started: September 11, 2020
First decision: October 27, 2020
Revised: November 5, 2020
Accepted: November 29, 2020
Article in press: November 29, 2020
Published online: December 21, 2020
Core Tip

Core Tip: Progressive familial intrahepatic cholestasis (PFIC) is an expanding group of genetically-based diseases caused by various autosomal recessive mutations which result in the inability to appropriately form and excrete bile from hepatocytes. There are three classic types of PFIC. Type 1 is caused by mutations of the ATP8B1 gene, encoding familial intrahepatic cholestasis 1. PFIC 2 is the result of mutations in the ABCB11 gene, reducing the apical membrane expression of bile salt export pump. PFIC 3 is caused by variations in the gene that encodes the multidrug resistance class 3 glycoprotein. With advances in DNA sequencing, new forms of this disease have been documented. Alterations in the NR1H4, tight junction protein 2, and MYO5B genes have been linked with new phenotypes of PFIC. Here, we provide a molecular and clinical overview of PFIC.