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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2015; 21(41): 11522-11541
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11522
Inflammatory status in human hepatic cirrhosis
María Martínez-Esparza, María Tristán-Manzano, Antonio J Ruiz-Alcaraz, Pilar García-Peñarrubia
María Martínez-Esparza, María Tristán-Manzano, Antonio J Ruiz-Alcaraz, Pilar García-Peñarrubia, Departamento de Bioquímica, Biología Molecular (B) e Inmunología, Facultad de Medicina, IMIB, Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain
Author contributions: Martínez-Esparza M contributed to study design, literature search, manuscript writing, figure design and final revision of the manuscript; Tristán-Manzano M contributed to the writing, figure design and final revision of the manuscript; Ruiz-Alcaraz AJ contributed to the writing, and final revision of the manuscript; García-Peñarrubia P contributed to study design, literature search, manuscript writing and final revision of the manuscript.
Supported by Grant 11926/PI/09 from the Fundación Séneca, Comunidad Autónoma de la Región de Murcia, Spain.
Conflict-of-interest statement: The authors have no conflict of interest to report.
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: María Martínez-Esparza, PhD, Professor in Immunology, Departamento de Bioquímica, Biología Molecular (B) e Inmunología, Facultad de Medicina, IMIB, Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain. maria@um.es
Telephone: +34-868-883989 Fax: +34-868-888601
Received: June 26, 2015
Peer-review started: June 29, 2015
First decision: July 13, 2015
Revised: July 31, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: November 7, 2015
Processing time: 129 Days and 17.9 Hours
Abstract

This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis.

Keywords: Inflammation; Macrophages; Cirrhosis; Alcohol; Hepatitis C virus; Cytokines; Liver

Core tip: This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis, avoiding results obtained from animal models. Liver cirrhosis is induced by the two main causes, infection with hepatitis C virus and chronic alcohol abuse. Detecting differences in the inflammatory status between both cirrhosis etiologies could be useful to identify specific targets for preventive and therapeutic intervention in each case.