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

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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

DOI 10.1136/gutjnl-2017-315691PMC PMC5889737

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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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Authors: Ibrahim, S. H., Hirsova, P., & Gores, G. J.
Affiliations: Mayo Clinic (US)
Charles University (CZ)
Corresponding author: Gores, Gregory J
ORCID: Ibrahim, Samar H
Hirsova, Petra
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
DOI: 10.1136/gutjnl-2017-315691
PMC: PMC5889737
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: green
www.ncbi.nlm.nih.gov
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 › Hepatology › 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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Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation

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