Cited by 166Alcohol Consumption and Health EffectsLiver physiology and pathologyLiver Disease Diagnosis and Treatment

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Pathogenesis of alcohol‐induced liver disease: Classical concepts and recent advances

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Seth, Devanshi, Haber, Paul S, Syn, Wing‐Kin, Diehl, Anna Mae, Day, Christopher P·2011·Journal of Gastroenterology and Hepatology

DOI 10.1111/j.1440-1746.2011.06756.x

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Abstract

Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking. ALD contributes to the bulk of liver disease burden worldwide. Progression of ALD is a multifactorial and multistep process that includes many genetic and environmental risk factors. The molecular pathogenesis of ALD involves alcohol metabolism and secondary mechanisms such as oxidative stress, endotoxin, cytokines and immune regulators. The histopathological manifestation of ALD occurs as an outcome of complex but controlled interactions between hepatic cell types. Hepatic stellate cells (HSCs) are the key drivers of fibrogenesis, but transformation of hepatocytes to myofibroblastoids also implicate parenchymal cells as playing an active role in hepatic fibrogenesis. Recent discoveries indicate that lipogenesis during the early stages of ALD is a risk for advancement to cirrhosis. Other recently identified novel molecules and physiological/cell signaling pathways include fibrinolysis, osteopontin, transforming growth factor‐β‐SMAD and hedgehog signaling, and involvement of novel cytokines in hepatic fibrogenesis. The observation that ALD and non‐alcoholic steatohepatitis share common pathways and genetic polymorphisms suggests operation of parallel pathogenic mechanisms. Future research involving genomics, epigenomics, deep sequencing and non‐coding regulatory elements holds promise to identify novel diagnostic and therapeutic targets for ALD. There is also a need for adequate animal models to study pathogenic mechanisms at the molecular level and targeted therapy.

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Authors: Seth, D., Haber, P. S., Syn, W., Diehl, A. M., & Day, C. P.
Affiliations: The University of Sydney (AU)
University of the Basque Country (ES)
Duke Medical Center (US)
Newcastle University (GB)
Corresponding author: Seth, Devanshi
ORCID: Seth, Devanshi
Haber, Paul S
Diehl, Anna Mae
Day, Christopher P
Venue: Journal of Gastroenterology and Hepatology
Publisher: Wiley
Published: 2011-06-14
Volume: 26
Issue: 7
Pages: 1089-1105
ISSN: 0815-9319 (ISSN-L)
1440-1746
DOI: 10.1111/j.1440-1746.2011.06756.x
OpenAlex: W1574483226
Cited by: 166
References: 219
Citations by year: 2025: 10 · 2024: 3 · 2023: 10 · 2022: 6 · 2021: 16 · 2020: 22 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 12 · 2015: 16 · 2014: 21 · 2013: 17 · 2012: 15
FWCI: 2.18
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Gastroenterology and Hepatology (publishedVersion)
PubMed (publishedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Newcastle University ePrints (Newcastle Univesity)
Funders: National Institutes of Health (5r37aa010154-20)
National Institute on Alcohol Abuse and Alcoholism (R37 AA-010154)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Keywords: alcoholic liver disease, pathogenesis, alcohol metabolism, oxidative stress, endotoxin, cytokines, immune regulation, hepatic stellate cells, hepatic fibrogenesis, myofibroblast transformation, lipogenesis, liver cirrhosis, fibrinolysis, osteopontin, TGF-β/Smad signaling, Hedgehog signaling, nonalcoholic steatohepatitis, genetic polymorphism, epigenomics, animal models, therapeutic target
MeSH terms: Alcohol Drinking, Ethanol, Animals, Humans, Liver Diseases, Alcoholic, Risk Factors, Global Health, Prevalence, Oxidative Stress

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Pathogenesis of alcohol‐induced liver disease: Classical concepts and recent advances

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