Editorial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2017; 23(5): 743-750
Published online Feb 7, 2017. doi: 10.3748/wjg.v23.i5.743
Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies
Youssef Alhmada, Denis Selimovic, Fadi Murad, Sarah-Lilly Hassan, Youssef Haikel, Mossaad Megahed, Matthias Hannig, Mohamed Hassan
Youssef Alhmada, Mohamed Hassan, Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, United States
Denis Selimovic, Graduate School of Dental Medicine, Department of Restorative Dentistry, Division of Oral Health Science, Hokkaido University, Sapporo 060-0808, Japan
Denis Selimovic, Matthias Hannig, Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, 66421 Homburg/Saar, Germany
Fadi Murad, Mohamed Hassan, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, United States
Sarah-Lilly Hassan, Mossaad Megahed, Clinic of Dermatology, University Hospital of Aachen, 52074 Aachen, Germany
Youssef Haikel, Mohamed Hassan, Institut National de la Santé et de la Recherché Médicale, U1121, 75019 Paris, France
Youssef Haikel, Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France
Author contributions: Alhmada Y, Selimovic D, Murad F and Hassan SL wrote part of the manuscript; Haikel Y, Megahed M, and Hannig M reviewed and edited the manuscript; Hassan M conceived the issues, and wrote and reviewed the manuscript.
Conflict-of-interest statement: The authors have no conflict of interests.
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: Dr. Mohamed Hassan, Department of Surgery, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, United States. dr.hassan@gmx.de
Telephone: +1-504-9889958 Fax: +1-504-9881874
Received: August 27, 2016
Peer-review started: August 31, 2016
First decision: October 20, 2016
Revised: November 17, 2016
Accepted: December 8, 2016
Article in press: December 8, 2016
Published online: February 7, 2017
Processing time: 148 Days and 10.7 Hours
Abstract

In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile acids in patients’ sera and tissues as a consequence of liver damage is considered the main cause of pruritus. In addition to their role in dietary lipid absorption, bile acids can trigger the activation of specific receptors, such as the G protein-coupled bile acid receptor (GPBA/ TGR5). These types of receptors are known to play a crucial role in the modulation of the systemic actions of bile acids. TGR5 expression in primary sensory neurons triggers the activation of the transient receptor potential vanilloid 1 (TRPV1) leading to the induction of pruritus by an unknown mechanism. Although the pathologic phenomenon of pruritus is common, there is no uniformly effective therapy available. Understanding the mechanisms regulating the occurrence of pruritus together with the conduction of large-scale clinical and evidence-based studies, may help to create a standard treatment protocol. This review focuses on the etiopathogenesis and treatment strategies of pruritus associated with chronic HCV infection.

Keywords: Hepatitis C virus; Pruritus; Cholestasis; Autotoxin; Lysophosphatidic acid; PI3 kinase

Core tip: Pruritus is a frequent symptom of chronic liver diseases. Chronic hepatitis C virus (HCV) infection can cause pruritus through both direct and indirect mechanisms. The direct mechanisms include induction of pro-inflammatory cytokines and chemokines as a consequence of the chronic HCV infection. Indirect mechanisms are associated with HCV-induced cholestasis leading to the accumulation of autotaxin, which is responsible for the conversion of lysophosphatidic choline into lysophosphatidic acid. This stimulates epidermal nerve endings leading to pruritus.