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Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments

Non-alcoholic steatohepatitis (NASH) develops from non-alcoholic fatty liver disease (NAFLD). Currently, around 25% of the population is estimated to have NAFLD, and 25% of NAFLD patients are estimated to have NASH. NASH is typically characterized by liver steatosis inflammation, and fibrosis driven...

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Autores principales: Peng, Cheng, Stewart, Alastair G., Woodman, Owen L., Ritchie, Rebecca H., Qin, Cheng Xue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745178/
https://www.ncbi.nlm.nih.gov/pubmed/33343375
http://dx.doi.org/10.3389/fphar.2020.603926
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author Peng, Cheng
Stewart, Alastair G.
Woodman, Owen L.
Ritchie, Rebecca H.
Qin, Cheng Xue
author_facet Peng, Cheng
Stewart, Alastair G.
Woodman, Owen L.
Ritchie, Rebecca H.
Qin, Cheng Xue
author_sort Peng, Cheng
collection PubMed
description Non-alcoholic steatohepatitis (NASH) develops from non-alcoholic fatty liver disease (NAFLD). Currently, around 25% of the population is estimated to have NAFLD, and 25% of NAFLD patients are estimated to have NASH. NASH is typically characterized by liver steatosis inflammation, and fibrosis driven by metabolic disruptions such as obesity, diabetes, and dyslipidemia. NASH patients with significant fibrosis have increased risk of developing cirrhosis and liver failure. Currently, NASH is the second leading cause for liver transplant in the United States. More importantly, the risk of developing hepatocellular carcinoma from NASH has also been highlighted in recent studies. Patients may have NAFLD for years before progressing into NASH. Although the pathogenesis of NASH is not completely understood, the current “multiple-hits” hypothesis suggests that in addition to fat accumulation, elevated oxidative and ER stress may also drive liver inflammation and fibrosis. The development of clinically relevant animal models and pharmacological treatments for NASH have been hampered by the limited understanding of the disease mechanism and a lack of sensitive, non-invasive diagnostic tools. Currently, most pre-clinical animal models are divided into three main groups which includes: genetic models, diet-induced, and toxin + diet-induced animal models. Although dietary models mimic the natural course of NASH in humans, the models often only induce mild liver injury. Many genetic and toxin + diet-induced models rapidly induce the development of metabolic disruption and serious liver injury, but not without their own shortcomings. This review provides an overview of the “multiple-hits” hypothesis and an evaluation of the currently existing animal models of NASH. This review also provides an update on the available interventions for managing NASH as well as pharmacological agents that are currently undergoing clinical trials for the treatment of NASH.
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spelling pubmed-77451782020-12-18 Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments Peng, Cheng Stewart, Alastair G. Woodman, Owen L. Ritchie, Rebecca H. Qin, Cheng Xue Front Pharmacol Pharmacology Non-alcoholic steatohepatitis (NASH) develops from non-alcoholic fatty liver disease (NAFLD). Currently, around 25% of the population is estimated to have NAFLD, and 25% of NAFLD patients are estimated to have NASH. NASH is typically characterized by liver steatosis inflammation, and fibrosis driven by metabolic disruptions such as obesity, diabetes, and dyslipidemia. NASH patients with significant fibrosis have increased risk of developing cirrhosis and liver failure. Currently, NASH is the second leading cause for liver transplant in the United States. More importantly, the risk of developing hepatocellular carcinoma from NASH has also been highlighted in recent studies. Patients may have NAFLD for years before progressing into NASH. Although the pathogenesis of NASH is not completely understood, the current “multiple-hits” hypothesis suggests that in addition to fat accumulation, elevated oxidative and ER stress may also drive liver inflammation and fibrosis. The development of clinically relevant animal models and pharmacological treatments for NASH have been hampered by the limited understanding of the disease mechanism and a lack of sensitive, non-invasive diagnostic tools. Currently, most pre-clinical animal models are divided into three main groups which includes: genetic models, diet-induced, and toxin + diet-induced animal models. Although dietary models mimic the natural course of NASH in humans, the models often only induce mild liver injury. Many genetic and toxin + diet-induced models rapidly induce the development of metabolic disruption and serious liver injury, but not without their own shortcomings. This review provides an overview of the “multiple-hits” hypothesis and an evaluation of the currently existing animal models of NASH. This review also provides an update on the available interventions for managing NASH as well as pharmacological agents that are currently undergoing clinical trials for the treatment of NASH. Frontiers Media S.A. 2020-12-03 /pmc/articles/PMC7745178/ /pubmed/33343375 http://dx.doi.org/10.3389/fphar.2020.603926 Text en Copyright © 2020 Peng, Stewart, Woodman, Ritchie and Qin http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Peng, Cheng
Stewart, Alastair G.
Woodman, Owen L.
Ritchie, Rebecca H.
Qin, Cheng Xue
Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments
title Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments
title_full Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments
title_fullStr Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments
title_full_unstemmed Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments
title_short Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments
title_sort non-alcoholic steatohepatitis: a review of its mechanism, models and medical treatments
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745178/
https://www.ncbi.nlm.nih.gov/pubmed/33343375
http://dx.doi.org/10.3389/fphar.2020.603926
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