Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2018; 24(47): 5297-5311
Published online Dec 21, 2018. doi: 10.3748/wjg.v24.i47.5297
Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy
Hu Li, Meng-Hao Huang, Jian-Dong Jiang, Zong-Gen Peng
Hu Li, Jian-Dong Jiang, Zong-Gen Peng, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Meng-Hao Huang, Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Jian-Dong Jiang, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Author contributions: All the authors contributed to the search and analysis of the literature and to the writing of the paper.
Supported by CAMS Innovation Fund for Medical Sciences, No. 2017-I2M-3-012; National Natural Science Foundation of China, No. 81773788 and 81621064; and National Mega-Project for “R&D for Innovative Drugs”, Ministry of Science and Technology, China, No. 2018ZX09711001-003-010.
Conflict-of-interest statement: No potential conflicts of interest.
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/
Corresponding author to: Zong-Gen Peng, PhD, Professor, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Tiantan Xili, Beijing 100050, China. pengzonggen@imb.pumc.edu.cn
Telephone: +86-10-63166129 Fax: +86-10-63017302
Received: October 19, 2018
Peer-review started: October 19, 2018
First decision: November 22, 2018
Revised: November 27, 2018
Accepted: November 30, 2018
Article in press: November 30, 2018
Published online: December 21, 2018
Abstract

Hepatitis C virus (HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals (DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with anti-inflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanisms of HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.

Keywords: Hepatitis C virus infection, Liver disease, Inflammatory pathogenesis, Anti-inflammatory and hepatoprotective therapy

Core tip: Inflammatory responses triggered by hepatitis C virus (HCV) infection lead to severe progressive liver diseases. Some inflammatory cytokines and chemokines may serve as biomarkers for the disease progression and therapeutic effect in chronic hepatitis C (CHC) patients. The inflammatory pathogenesis in HCV-infected patients is complicated, including classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals (DAAs) are not sufficient to block the uncontrolled inflammation and disease progression in severe CHC patients. Therefore, coupling with anti-inflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for advanced HCV-infected patients during or after treatment with DAAs.