Kanda T, Sasaki-Tanaka R, Yokoo T, Hayashi K, Kamimura H, Tsuchiya A, Terai S. Cholestasis in hepatitis E virus infection. World J Hepatol 2025; 17(4): 99899 [DOI: 10.4254/wjh.v17.i4.99899]
Corresponding Author of This Article
Tatsuo Kanda, MD, PhD, Professor, Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minamiuonuma 949-7302, Niigata, Japan. kandatatsuo@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
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/
Tatsuo Kanda, Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minamiuonuma 949-7302, Niigata, Japan
Reina Sasaki-Tanaka, Takeshi Yokoo, Kazunao Hayashi, Hiroteru Kamimura, Atsunori Tsuchiya, Shuji Terai, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan
Author contributions: Kanda T and Sasaki-Tanaka R designed the overall concept and outline of the manuscript and wrote the paper; Kanda T, Sasaki-Tanaka R, Yokoo T, Hayashi K, Kamimura H, Tsuchiya A, and Terai S contributed critical revision of the manuscript for important intellectual content; all authors have read and approved the final manuscript.
Supported by the Japan Agency for Medical Research and Development (AMED), No. JP24fk0210132 (Kanda T, Sasaki-Tanaka R and Terai S); and the JSPS KAKENHI, No. JP23K15055 (Sasaki-Tanaka R).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tatsuo Kanda, MD, PhD, Professor, Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minamiuonuma 949-7302, Niigata, Japan. kandatatsuo@gmail.com
Received: August 2, 2024 Revised: September 21, 2024 Accepted: October 9, 2024 Published online: April 27, 2025 Processing time: 265 Days and 23.2 Hours
Abstract
Hepatitis E virus (HEV) infection causes acute hepatitis, chronic hepatitis, particularly in compromised hosts, and various extrahepatic manifestations. HEV infection is reportedly associated with biliary-pancreatic diseases, such as gallstones, cholangitis, choledocholithiasis, and acute pancreatitis. Severe jaundice and prolonged cholestasis are also atypical manifestations of HEV infection. The mechanism and genes involved in cholestasis, namely sinusoidal uptake of blood, bile salt synthesis and secretion from hepatocytes to the canaliculus, have been elucidated. HEV infection triggers severe jaundice and prolonged cholestasis in patients with genetic variants in adenosine triphosphatase phospholipid transporting 8B1, adenosine triphosphate-binding cassette (ABC) protein B4, ABCB11, Myosin VB, and/or farnesoid X receptor (FXR/NR1H4). Although prolonged cholestasis associated with these gene mutations does not seem to be specific to HEV infection, these mutations may be risk factors related to the severity of HEV infection. The use of the pregnane X receptor agonist rifampicin and the peroxisome proliferator-activated receptor activator bezafibrate may be useful for the treatment of cholestasis. These studies provide new insights into understanding the mechanisms of severe jaundice and prolonged cholestasis caused by HEV infection.
Core Tip: Hepatitis E virus (HEV) infection triggers severe jaundice and prolonged cholestasis in patients with genetic variants in adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1), adenosine triphosphate-binding cassette (ABC) protein B4, ABCB11, Myosin VB and/or farnesoid X receptor (FXR/NR1H4). Genomic mutations associated with hepatocanalicular transporter proteins occasionally cause cholestasis. HEV infection may trigger severe jaundice and prolonged cholestasis in patients with these genomic mutations.
