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Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese
Abstract
Background & aims Morbid obesity is frequently associated with low grade systemic inflammation, increased macrophage accumulation in adipose tissue (AT), obstructive sleep apnea (OSA), and nonalcoholic fatty liver disease (NAFLD). It has been suggested that chronic intermittent hypoxia (CIH) resulting from OSA could be an independent factor for early stage of NAFLD in addition to other well-recognized factors (dyslipidemia or insulin resistance). Moreover, macrophage accumulation in AT is associated with local hypoxia in fat tissue. We hypothesized that the association between CIH and morbid obesity could exert additional specific deleterious effects both in the liver and adipose tissues.Methods One hundred and one morbidly obese subjects were prospectively recruited and underwent bariatric surgery during which a liver needle biopsy as well as surgical subcutaneous and omental AT biopsies were obtained. Oxygen desaturation index (ODI) quantified the severity of nocturnal CIH.Results Histopathologic analysis of liver biopsies demonstrated that NAFLD lesions (ballooning of hepatocytes, lobular inflammation), NAFLD activity score (NAS), and fibrosis were significantly more severe in patients with the highest ODI tertile (p values ≤0.001 for all hepatic lesions). In multivariate analysis, after adjustment for age, obesity, and insulin resistance status, CIH remained independently associated with hepatic fibrosis, fibroinflammation, and NAS. By contrast, no association was found between CIH, macrophage accumulation, and adipocytes size in both subcutaneous and omental adipose tissue.Conclusions In morbidly obese patients, CIH was strongly associated with more severe liver injuries but did not worsen obesity induced macrophage accumulation in adipose tissue depots.
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“Both OSA and PCOS are associated with MASLD,”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [65]
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“and several studies suggest OSA is also associated with more advanced MASLD/MASH histology, 64,65”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [65]
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Metadata
- Authors
- Aron-Wisnewsky, J., Minville, C., Tordjman, J., Lévy, P., Bouillot, J.-L., Basdevant, A., Bedossa, P., Clément, K., & Pépin, J.-L.
- Affiliations
- Inserm (FR)
- Hôpital Cochin (FR)
- Corresponding author
- Pépin, Jean-Louis
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 56
- Issue
- 1
- Pages
- 225-233
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2020505247
- Cited by
- 255
- References
- 55
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 19 · 2023: 14 · 2022: 21 · 2021: 16 · 2020: 15 · 2019: 18 · 2018: 18 · 2017: 13 · 2016: 19 · 2015: 25 · 2014: 24 · 2013: 20 · 2012: 10
- FWCI
- 13.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Physiology (medical) › Obstructive Sleep Apnea Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- chronic intermittent hypoxia, non-alcoholic fatty liver disease, morbid obesity, obstructive sleep apnea, liver fibrosis, hepatic steatosis, oxygen desaturation index, bariatric surgery, liver biopsy, NAFLD activity score, fibroinflammation
- MeSH terms
- Adipose Tissue, Adult, Hypoxia, Chronic Disease, Fatty Liver, Female, Humans, Insulin Resistance, Liver, Male, Middle Aged, Obesity, Morbid, Prospective Studies, Risk Factors, Cohort Studies, Sleep Apnea, Obstructive, Bariatric Surgery, Non-alcoholic Fatty Liver Disease
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