Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 15, 2015; 6(4): 90-98
Published online Nov 15, 2015. doi: 10.4291/wjgp.v6.i4.90
Alcoholic hepatitis: The pivotal role of Kupffer cells
Duminda B Suraweera, Ashley N Weeratunga, Robert W Hu, Stephen J Pandol, Richard Hu
Duminda B Suraweera, Department of Medicine, Olive View-UCLA Medical Center, Los Angeles, CA 91342, United States
Ashley N Weeratunga, Creighton University School of Medicine, Omaha, NE 68102, United States
Robert W Hu, College of Arts and Sciences, the University of Pennsylvania, Philadelphia, PA 19104, United States
Robert W Hu, Stephen J Pandol, Department of Gastroenterology and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Richard Hu, Department of Gastroenterology, Olive View-UCLA Medical Center and David Geffen School of Medicine at UCLA, Los Angeles, CA 91342, United States
Author contributions: Suraweera DB designed the project, reviewed the articles and wrote the paper; Weeratunga AN and Hu RW reviewed the articles and analyzed data; Pandol SJ edited and reviewed the articles; Hu R contributed to developing the concept, editing and reviewing the article.
Conflict-of-interest statement: None of the authors of this paper have any conflict of interest to declare.
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: Richard Hu, MD, Department of Gastroenterology, Olive View-UCLA Medical Center and David Geffen School of Medicine at UCLA, 14445 Olive View Dr., 2B-182, Los Angeles, CA 91342, United States. richardhu@mednet.ucla.edu
Telephone: +1-818-3643205 Fax: +1-818-3644573
Received: May 26, 2015
Peer-review started: May 27, 2015
First decision: July 3, 2015
Revised: July 27, 2015
Accepted: September 7, 2015
Article in press: September 8, 2015
Published online: November 15, 2015

Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis (AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides (LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called toll-like receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis.

Keywords: Alcoholic liver disease, Alcoholic hepatitis, Macrophages, Kupffer cells

Core tip: In this editorial we provide critical comments on the pivotal role of Kupffer cells on the development of alcoholic hepatitis with a focus on the pro-inflammatory as well as the anti-inflammatory pathways. We propose that the anti-inflammatory pathway should be further explored as a potential alternative for novel treatment strategies. This editorial is significant as it provides a platform for the future basic and clinical research in elucidating the pathogenesis and developing the management strategies of this common clinical pathology - alcoholic hepatitis.