Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2020; 12(8): 423-435
Published online Aug 27, 2020. doi: 10.4254/wjh.v12.i8.423
Review: Pathogenesis of cholestatic liver diseases
Raquel T Yokoda, Eduardo A Rodriguez
Raquel T Yokoda, Department of Anatomic and Clinical Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, United States
Eduardo A Rodriguez, Department of Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, UT 84132, United States
Author contributions: Yokoda RT and Rodriguez EA wrote the paper and approved the final version.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
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: Eduardo A Rodriguez, FACP, MD, Assistant Professor, Department of Gastroenterology, Hepatology and Nutrition, University of Utah, 30 N 1900 E, Room 4R118, Salt Lake City, UT 84132, United States.
Received: May 6, 2020
Peer-review started: May 6, 2020
First decision: May 24, 2020
Revised: June 7, 2020
Accepted: August 1, 2020
Article in press: August 1, 2020
Published online: August 27, 2020

Cholestatic liver diseases (CLD) begin to develop after an impairment of bile flow start to affect the biliary tree. Cholangiocytes actively participate in the liver response to injury and repair and the intensity of this reaction is a determinant factor for the development of CLD. Progressive cholangiopathies may ultimately lead to end-stage liver disease requiring at the end orthotopic liver transplantation. This narrative review will discuss cholangiocyte biology and pathogenesis mechanisms involved in four intrahepatic CLD: Primary biliary cholangitis, primary sclerosing cholangitis, cystic fibrosis involving the liver, and polycystic liver disease.

Keywords: Cholestasis, Cholangitis, Epigenomics, Immunogenetics, Pathogenesis, Bile acid

Core tip: Several factors can condition bile flow derangements including environmental triggering factors, bile transport obstruction and conditions that alter bile concentration. Sustained pro inflammatory signaling associated with genetic and/or epigenetic dysregulation can condition a chronic dysfunctional state that can lead to a fibrogenic state with loss of homeostasis and sometimes malignant transformation.