Chronic Intermittent Hypoxia and MASLD in Obstructive Sleep Apnea: A Critical Appraisal of Mechanistic and Causal Evidence
10 affiliations
- 1Doctoral School, University of Medicine and Pharmacy, 200349 Craiova, Romania
- 2Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- 3Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Midwives and Nursing, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- 4Department of Internal Medicine—Internal Medicine, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- 5Department of Oro-Dental Prevention and Oral Health, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- 6Research Centre in Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- 7Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- 8Faculty of Medicine, University of Medicine and Pharmacy “Iuliu Haţieganu” Cluj-Napoca, 400012 Cluj-Napoca, Romania
- 9Department of Obstetrics-Gynecology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- 10Department of Medical Semiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Abstract
Obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist and share a common cardiometabolic substrate through a shared cardiometabolic substrate. This narrative review critically appraises the epidemiological, experimental, and interventional evidence proposed to link chronic intermittent hypoxia (CIH) and sleep fragmentation to hepatic steatosis, steatohepatitis, and fibrosis. We summarize the candidate mechanisms, including mitochondrial oxidative stress, hypoxia-inducible factor 1-alpha signaling, sympathetically driven lipolysis, and Kupffer and stellate cell activation and then examine the limits of the evidence supporting them: hypoxia-induced hypophagia and the scarcity of pair-fed controls in rodent models, species differences in the physiological response to hypoxia, publication bias, common-cause confounding by age and systemic inflammation, and the rarity of progressive liver disease in lean patients with anatomically driven OSA. We further review non-invasive diagnostic tools, polysomnographic hypoxemia indices, transient elastography, METS-IR, FIB-4, and emerging biomarkers, such as omentin-1 and follistatin-like 1, that enable bidirectional screening between sleep and hepatology clinics. Finally, we discuss therapeutic strategies, including continuous positive airway pressure, structured weight loss, and incretin-based pharmacotherapy (GLP-1 and dual GIP/GLP-1 receptor agonists), highlighting recent phase 3 evidence for tirzepatide in OSA and semaglutide in metabolic dysfunction-associated steatohepatitis. Current evidence supports CIH as a context-dependent amplifier of liver injury in patients with pre-existing metabolic dysfunction rather than as an established independent cause of MASH. This interpretation still justifies integrated screening and treatment pathways, while identifying the study designs needed to test causality directly.
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BibTeX
@article{simeanu2026chronic,
title = {{Chronic Intermittent Hypoxia and MASLD in Obstructive Sleep Apnea: A Critical Appraisal of Mechanistic and Causal Evidence}},
author = {Georgiana-Mihaela Cebuc Simeanu and Ioana-Gabriela Dragne and Adina Mitrea and Diana Clenciu and Diana-Cristina Protasiewicz-Timofticiuc and Alina-Liliana Popa and Denisa-Maria Mitroi and Bianca-Florentina Pîrvu and Ion-Cristian Efrem and Adina Dorina Glodeanu and Adina-Andreea Mirea and Adela-Gabriela Ștefan and Maria-Magdalena Roșu and Theodora-Claudia Radu-Gheonea and Beatrice-Elena Vladu and Ana-Maria Efrem and Lorena-Anda Dijmarescu and Mircea-Catalin Fortofoiu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209372},
url = {https://www.mdpi.com/1422-0067/27/20/9372},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Chronic Intermittent Hypoxia and MASLD in Obstructive Sleep Apnea: A Critical Appraisal of Mechanistic and Causal Evidence
AU - Georgiana-Mihaela Cebuc Simeanu
AU - Ioana-Gabriela Dragne
AU - Adina Mitrea
AU - Diana Clenciu
AU - Diana-Cristina Protasiewicz-Timofticiuc
AU - Alina-Liliana Popa
AU - Denisa-Maria Mitroi
AU - Bianca-Florentina Pîrvu
AU - Ion-Cristian Efrem
AU - Adina Dorina Glodeanu
AU - Adina-Andreea Mirea
AU - Adela-Gabriela Ștefan
AU - Maria-Magdalena Roșu
AU - Theodora-Claudia Radu-Gheonea
AU - Beatrice-Elena Vladu
AU - Ana-Maria Efrem
AU - Lorena-Anda Dijmarescu
AU - Mircea-Catalin Fortofoiu
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209372
UR - https://www.mdpi.com/1422-0067/27/20/9372
AB - Obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist and share a common cardiometabolic substrate through a shared cardiometabolic substrate. This narrative review critically appraises the epidemiological, experimental, and interventional evidence proposed to link chronic intermittent hypoxia (CIH) and sleep fragmentation to hepatic steatosis, steatohepatitis, and fibrosis. We summarize the candidate mechanisms, including mitochondrial oxidative stress, hypoxia-inducible factor 1-alpha signaling, sympathetically driven lipolysis, and Kupffer and stellate cell activation and then examine the limits of the evidence supporting them: hypoxia-induced hypophagia and the scarcity of pair-fed controls in rodent models, species differences in the physiological response to hypoxia, publication bias, common-cause confounding by age and systemic inflammation, and the rarity of progressive liver disease in lean patients with anatomically driven OSA. We further review non-invasive diagnostic tools, polysomnographic hypoxemia indices, transient elastography, METS-IR, FIB-4, and emerging biomarkers, such as omentin-1 and follistatin-like 1, that enable bidirectional screening between sleep and hepatology clinics. Finally, we discuss therapeutic strategies, including continuous positive airway pressure, structured weight loss, and incretin-based pharmacotherapy (GLP-1 and dual GIP/GLP-1 receptor agonists), highlighting recent phase 3 evidence for tirzepatide in OSA and semaglutide in metabolic dysfunction-associated steatohepatitis. Current evidence supports CIH as a context-dependent amplifier of liver injury in patients with pre-existing metabolic dysfunction rather than as an established independent cause of MASH. This interpretation still justifies integrated screening and treatment pathways, while identifying the study designs needed to test causality directly.
SN - 1422-0067
ER -