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Int. J. Mol. Sci. 2014, 15(5), 7352-7379; doi:10.3390/ijms15057352

Molecular Mechanisms and New Treatment Strategies for Non-Alcoholic Steatohepatitis (NASH)

* ,
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
* Author to whom correspondence should be addressed.
Received: 1 March 2014 / Revised: 28 March 2014 / Accepted: 10 April 2014 / Published: 29 April 2014
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
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Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD), in which most patients exhibit non-progressive, non-alcoholic fatty liver (NAFL) attributable to simple steatosis. Multiple hits, including genetic differences, fat accumulation, insulin resistance and intestinal microbiota changes, account for the progression of NASH. NAFLD is strongly associated with obesity, which induces adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level, which in turn induces hepatic steatosis, inflammation and fibrosis. Among these factors, gut microbiota are acknowledged as having an important role in initiating this multifactorial disease. Oxidative stress is considered to be a key contributor in the progression from NAFL to NASH. Macrophage infiltration is apparent in NAFL and NASH, while T-cell infiltration is apparent in NASH. Although several clinical trials have shown that antioxidative therapy with vitamin E can effectively control hepatitis pathology in the short term, the long-term effects remain obscure and have often proved to be ineffective in many other diseases. Several long-term antioxidant protocols have failed to reduce mortality. New treatment modalities that incorporate current understanding of NAFLD molecular pathogenesis must be considered.
Keywords: non-alcoholic fatty liver; non-alcoholic steatohepatitis; microbiome; oxidative stress non-alcoholic fatty liver; non-alcoholic steatohepatitis; microbiome; oxidative stress
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Takaki, A.; Kawai, D.; Yamamoto, K. Molecular Mechanisms and New Treatment Strategies for Non-Alcoholic Steatohepatitis (NASH). Int. J. Mol. Sci. 2014, 15, 7352-7379.

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