Evolving concepts in the pathogenesis of NASH: Beyond steatosis and inflammation

Peverill, William, Powell, Lawrie W. and Skoien, Richard (2014) Evolving concepts in the pathogenesis of NASH: Beyond steatosis and inflammation. International Journal of Molecular Sciences, 15 5: 8591-8638. doi:10.3390/ijms15058591


Author Peverill, William
Powell, Lawrie W.
Skoien, Richard
Title Evolving concepts in the pathogenesis of NASH: Beyond steatosis and inflammation
Journal name International Journal of Molecular Sciences   Check publisher's open access policy
ISSN 1422-0067
Publication date 2014-05-14
Sub-type Critical review of research, literature review, critical commentary
DOI 10.3390/ijms15058591
Open Access Status DOI
Volume 15
Issue 5
Start page 8591
End page 8638
Total pages 48
Place of publication Basel, Switzerland
Publisher M D P I AG
Language eng
Abstract Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis and inflammation and, in some patients, progressive fibrosis leading to cirrhosis. An understanding of the pathogenesis of NASH is still evolving but current evidence suggests multiple metabolic factors critically disrupt homeostasis and induce an inflammatory cascade and ensuing fibrosis. The mechanisms underlying these changes and the complex inter-cellular interactions that mediate fibrogenesis are yet to be fully elucidated. Lipotoxicity, in the setting of excess free fatty acids, obesity, and insulin resistance, appears to be the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence contribute to activation of the inflammasome via a variety of intra- and inter-cellular signalling mechanisms leading to fibrosis. Current evidence suggests that periportal components, including the ductular reaction and expansion of the hepatic progenitor cell compartment, may be involved and that the Th17 response may mediate disease progression. This review aims to provide an overview of the pathogenesis of NASH and summarises the evidence pertaining to key mechanisms implicated in the transition from steatosis and inflammation to fibrosis. Currently there are limited treatments for NASH although an increasing understanding of its pathogenesis will likely improve the development and use of interventions in the future.
Keyword Fibrosis
Immune response
Inflammation
Lipotoxicity
Non alcoholic steatohepatitis
Pathogenesis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
Official 2015 Collection
School of Medicine Publications
 
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