Cited by 278Liver Disease Diagnosis and TreatmentLiver physiology and pathologyDrug-Induced Hepatotoxicity and Protection

Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation

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Ibrahim, Samar H, Hirsova, Petra, Gores, Gregory J·2018·Gut

Abstract

A subset of patients with non-alcoholic fatty liver disease develop an inflammatory condition, termed non-alcoholic steatohepatitis (NASH). NASH is characterised by hepatocellular injury, innate immune cell-mediated inflammation and progressive liver fibrosis. The mechanisms whereby hepatic inflammation occurs in NASH remain incompletely understood, but appear to be linked to the proinflammatory microenvironment created by toxic lipid-induced hepatocyte injury, termed lipotoxicity. In this review, we discuss the signalling pathways induced by sublethal hepatocyte lipid overload that contribute to the pathogenesis of NASH. Furthermore, we will review the role of proinflammatory, proangiogenic and profibrotic hepatocyte-derived extracellular vesicles as disease biomarkers and pathogenic mediators during lipotoxicity. We also review the potential therapeutic strategies to block the feed-forward loop between sublethal hepatocyte injury and liver inflammation.

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Crossref · 10.1136/gutjnl-2017-315691

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  • Caloric overload, steatosis, oxidative stress, ER stress and hepatocyte lipoapoptosis represent first steps in cell-cell communication, triggering the fibroinflammatory cycle.

    “Caloric overload, steatosis, oxidative stress, ER stress and hepatocyte ‘lipoapotosis’ represent first steps in cell-cell communication, triggering the fibroinflammatory cycle.13,23”

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Authors
Ibrahim, S. H., Hirsova, P., & Gores, G. J.
Affiliations
  • Mayo Clinic (US)
  • Charles University (CZ)
Corresponding author
Gores, Gregory J
Venue
Gut
Publisher
BMJ
Published
2018-01-24
Volume
67
Issue
5
Pages
963-972
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
OpenAlex
W2784619339
Cited by
278
References
89
Citations by year
2026: 20 · 2025: 26 · 2024: 28 · 2023: 29 · 2022: 37 · 2021: 50 · 2020: 43 · 2019: 28 · 2018: 17
FWCI
4.93
Type
journal article
Language
en
Open access
Locations
  • Gut (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Mayo Clinic
  • Gilead Sciences
  • MH CZ–DRO
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • North American Society of Pediatric Gastroenterology Hepatology and Nutrition Young Investigator Award/Nestle Nutrition Award
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, lipotoxicity, lipid overload, liver inflammation, liver fibrosis, disease biomarkers, treatment options
MeSH terms
Animals, Hepatitis, Humans, Lipids, Liver, Signal Transduction, Hepatocytes, Non-alcoholic Fatty Liver Disease

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