Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2018; 10(1): 1-7
Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.1
Role of inflammatory response in liver diseases: Therapeutic strategies
José A Del Campo, Paloma Gallego, Lourdes Grande
José A Del Campo, Paloma Gallego, Lourdes Grande, Department of Digestive Diseases, Valme University Hospital and CIBERehd, Sevilla 41014, Spain
Author contributions: Del Campo JA designed the study and drafted the manuscript; Gallego P and Grande L drafted the manuscript and designed the figure.
Supported by Andalusian Government, No. PI0892-2012; Instituto de Salud Carlos III, PI14/01349 co-financed by the European Regional Development Fund (ERDF); JA Del Campo supported by Nicolás Monardes Program from Servicio Andaluz de Salud (SAS).
Conflict-of-interest statement: Authors declare no 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:
Correspondence to: José A Del Campo, PhD, Department of Digestive Diseases, Valme University Hospital and CIBERehd, Avda. Bellavista s/n, Sevilla 41014, Spain.
Telephone: +34-955-015485 Fax: +34-955-015485
Received: November 8, 2017
Peer-review started: November 9, 2017
First decision: December 4, 2017
Revised: December 21, 2017
Accepted: January 15, 2018
Article in press: January 15, 2018
Published online: January 27, 2018

Inflammation and tumorigenesis are tightly linked pathways impacting cancer development. Inflammasomes are key signalling platforms that detect pathogenic microorganisms, including hepatitis C virus (HCV) infection, and sterile stressors (oxidative stress, insulin resistance, lipotoxicity) able to activate pro-inflammatory cytokines interleukin-1β and IL-18. Most of the inflammasome complexes that have been described to date contain a NOD-like receptor sensor molecule. Redox state and autophagy can regulate inflammasome complex and, depending on the conditions, can be either pro- or anti-apoptotic. Acute and chronic liver diseases are cytokine-driven diseases as several proinflammatory cytokines (IL-1α, IL-1β, tumor necrosis factor-alpha, and IL-6) are critically involved in inflammation, steatosis, fibrosis, and cancer development. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and highlighting this pathway in the pathogenesis of non-alcoholic fatty liver disease. On the other hand, HCV infection is the primary catalyst for progressive liver disease and development of liver cancer. It is well established that HCV-induced IL-1β production by hepatic macrophages plays a critical and central process that promotes liver inflammation and disease. In this review, we aim to clarify the role of the inflammasome in the aggravation of liver disease, and how selective blockade of this main pathway may be a useful strategy to delay fibrosis progression in liver diseases.

Keywords: Caspase-1, Fibrosis, Hepatitis C virus, Inflammasome, Interleukin-1α, Interleukin-1β, Liver disease, Non-alcoholic fatty liver disease, NLRP3, Tumor necrosis factor-alpha

Core tip: Inflammasomes are newly recognized vital players in innate immunity. Several factors have been identified able to activate the NLRP3 inflammasome. Inappropriate activation of NLRP3 can contribute to the onset and progression of various diseases, particularly age-related diseases. It is well established that hepatitis C virus infection plays a critical role in the promotion of liver inflammation and disease, inducing the production of IL-1β and the activation of NLRP3. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and lately, hepatocellular carcinoma. In non-alcoholic fatty liver disease, the regulation of inflammation processes may prevent the progression of non-alcoholic steatohepatitis to fibrosis.