Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2018; 24(45): 5063-5075
Published online Dec 7, 2018. doi: 10.3748/wjg.v24.i45.5063
Alcoholic liver disease: Utility of animal models
Arantza Lamas-Paz, Fengjie Hao, Leonard J Nelson, Maria Teresa Vázquez, Santiago Canals, Manuel Gómez del Moral, Eduardo Martínez-Naves, Yulia A Nevzorova, Francisco Javier Cubero
Arantza Lamas-Paz, Fengjie Hao, Eduardo Martínez-Naves, Francisco Javier Cubero, Department of Immunology, Ophthalmology and ORL, Complutense University School of Medicine, Madrid 28040, Spain
Arantza Lamas-Paz, Fengjie Hao, Eduardo Martínez-Naves, Yulia A Nevzovova, Francisco Javier Cubero, 12 de Octubre Health Research Institute (imas12), Madrid 28041, Spain
Leonard J Nelson, Institute for Bioengineering (IBioE), School of Engineering, Faraday Building, The University of Edinburgh, Edinburgh EH9 3 JL, Scotland, United Kingdom
Maria Teresa Vázquez, Department of Human Anatomy and Embryology, Complutense University School of Medicine, Madrid 28040, Spain
Santiago Canals, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, San Juan de Alicante 03550, Spain
Manuel Gómez del Moral, Department of Cell Biology, Complutense University School of Medicine, Madrid 28040, Spain
Yulia A Nevzorova, Department of Genetics, Physiology and Microbiology, Faculty of Biology, Universidad Complutense, Madrid 28040, Spain
Yulia A Nevzorova, Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52062, Germany
Author contributions: Lamas-Paz A and Hao F equally contributed to the manuscript writing and figure design; Nelson LJ, Vázquez MT, Canals S, Gómez del Moral M and Martínez-Naves E critiqued the manuscript, checked English language and provided fundamental guidance. Nevzorova YA and Cubero FJ outlined and corrected the review and provided guidance.
Supported by the MINECO Retos, No. SAF2016-78711 and SAF2017-87919R; EXOHEP-CM, No. S2017/BMD-3727; the AMMF Cholangiocarcinoma Charity, No. 2018/117; the COST Action, No. CA17112; Ramón y Cajal, No. RYC-2014-15242 and No. RYC-2015-17438; grant of ERAB, No. EA 14/18; Gilead Liver Research Scholar 2018, No. 44/2018; Ministerio de Sanidad, Servicios Sociales e Igualdad, No. 2017I065; and the UCM group “Lymphocyte Immunobiology”, No. 920631 (imas12-associated, Ref. IBL-6). German Research Foundation (SFB/TRR57/P04 and DFG NE 2128/2-1); Interdisciplinary Center for Clinical Research from the Faculty of Medicine at RWTH Aachen University (IZKF/E8-2).
Correspondence author to: Francisco Javier Cubero, BSc, MSc, PhD, Assistant Professor, Department of Immunology, Ophthalmology and ORL, Complutense University School of Medicine, c/Doctor Severo Ochoa 9, Madrid 28040, Spain. fcubero@ucm.es
Telephone: +34-91-3941385 Fax: +34-91-394164
Received: October 19, 2018
Peer-review started: October 19, 2018
First decision: November 1, 2018
Revised: November 8, 2018
Accepted: November 9, 2018
Article in press: November 9, 2018
Published online: December 7, 2018
Abstract

Alcoholic liver disease (ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

Keywords: Steatohepatitis, Cirrhosis, Hepatocellular carcinoma, Alcoholic liver disease, Reactive oxygen species

Core tip: Alcoholism is now considered a global health issue. Although significant progress has been made in our understanding of the mechanisms and pathology of alcoholic liver disease (ALD), many features of ALD remain unidentified - requiring further investigation with improved animal models that more effectively emulate human ALD. In this Review, we provide an update on the prevalence, current and emerging experimental models, as well as the pathophysiology of ALD.