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Nonalcoholic Fatty Liver Disease: Pathogenesis and the Role of Antioxidants
Abstract
Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.
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“NAC counters ROS in nonalcoholic steatohepatitis, a disorder often associated with type 2 diabetes and characterized by mitochondrial ROS production (214).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [214]
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Association between dietary glycemic index and liver enzymes level among apparently healthy adults
Moshtaq, M. A., Rahimi, M. H., Mollahosseini, M., Khorraminezhad, L., Maghbooli, Z., Mirzaei, K., Pooyan, S., & Setayesh, L. (2019) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2019.03.013 · Cited by 4
Recent advances in the treatment of non-alcoholic fatty liver disease with astragaloside IV
Wang, H., Jiang, Y., Wang, S., Lu, C., Tang, L., Gu, T., & Shu, S. (2025) · Acta Pharmaceutica · doi:10.2478/acph-2025-0022 · Cited by 3
“Medium-and long-chain fatty acids are primarily oxidised in the mitochondria, whereas very long-chain fatty acids (VLCFAs) are almost entirely metabolised through β-oxidation in peroxisomes (52), a process that generates reactive oxygen species (ROS) such as hydrogen peroxide.”
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Sakai, T. I. K. (2015) · Journal of Diabetes & Metabolism · doi:10.4172/2155-6156.1000598 · Cited by 3
“The pathogenesis of non-alcoholic hepatitis is considered by two-hit theory [16,17].”
BackgroundThe consequences of poor dietary patterns on the proliferation of non-alcoholic fatty liver disease
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“After three months of therapy, all participants had transaminases that were normal (Mehta et al., 2002).”
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Metabolic Disease and Hepatocellular Carcinoma
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“NASH is reported to be present in 3% of the adult population in the United States, a rate twice that of chronic hepatitis C (HCV) ( 34 ).”
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Effects of Polyphenol-Rich Foods on Human Health
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Metadata
- Authors
- Mehta, K., Van Thiel, D. H., Shah, N., & Mobarhan, S.
- Affiliations
- Loyola University Medical Center (US)
- Drs. Mehta, VanThiel, Shah, and Mobarhan arewith the Division of Gastroenterology, Hepatology, and Nutrition, Loyola University Medical Center, 2160 South First Avenue, Maywood, Illinois 60153, USA.
- ORCID
- Shah, Nikunj
- Venue
- Nutrition Reviews
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-09-01
- Volume
- 60
- Issue
- 9
- Pages
- 289-293
- ISSN
- 0029-6643 (ISSN-L)
- 1753-4887
- OpenAlex
- W2123856468
- Cited by
- 250
- References
- 0
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 11 · 2017: 7 · 2016: 18 · 2015: 16 · 2014: 20 · 2013: 12 · 2012: 8
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nutrition Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatic steatosis, liver fibrosis, liver cirrhosis, insulin resistance, two-hit theory, oxidative stress, reactive oxygen species, mitochondrial reactive oxygen species, antioxidants, vitamin E, N-acetylcysteine, betaine, obesity, type 2 diabetes, hyperlipidemia
- MeSH terms
- Antioxidants, Fatty Liver, Humans
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