{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:47:25Z","timestamp":1782276445650,"version":"3.54.5"},"reference-count":30,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which causes numerous metabolic changes, leading to non-alcoholic fatty liver disease (NAFLD). Our study explored the suggested role of hypoxia-inducible factor 1-\u03b1 (HIF-1\u03b1) in the pathophysiological mechanisms linking OSA with NAFLD. Methods: This case-control study was conducted at the Sleep Disorders Unit at Qena University Hospital from March 2022 to October 2023, including 64 subjects (48 OSA patients; in a secondary analysis, OSA patients were further stratified according to the presence or absence of NAFLD\u201316 controls) who were subjected to a polysomnography (PSG) for apnea hypopnea index (AHI) and transient elastography for controlled attenuation parameter (CAP) score and liver stiffness measurement (LSM). Serum levels of HIF 1-\u03b1, fasting blood glucose, and fasting insulin were measured. Results: HIF-1\u03b1 level showed the highest significant value was in the severe group (p = 0.001). Additionally, the severe group had the highest LSM compared to the other groups (p = 0.032). OSA patients with NAFLD, compared to OSA patients without NAFLD, showed significantly higher BMI (42.74 vs. 29.11 kg\/m2, p &lt; 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) mean score (3.92 vs. 1.21, p &lt; 0.0001), HIF-1\u03b1 level (6.01 vs. 2.14 ng\/L, p = 0.045), and the LSM score (5.55 vs. 3.85 kPa, p &lt; 0.001). HIF-1\u03b1 showed significant positive correlations with AHI (r = 0.515, p &lt; 0.001), waist circumference WC (r = 0.291, p = 0.045), HSI (r = 0.3, p = 0.038), and CAP score (r = 0.288, p = 0.047). Conclusions: Although serum HIF-1\u03b1 levels were significantly higher in OSA patients with NAFLD and correlated with indices of hepatic steatosis, HIF-1\u03b1 was not identified as an independent predictor of NAFLD after adjustment for metabolic confounders, suggesting a potential role of hypoxia-responsive pathways in pathophysiology of NAFLD in OSA.<\/jats:p>","DOI":"10.3390\/jcm15134861","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"4861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Hypoxia-Inducible Factor-1\u03b1 in the Pathophysiology of Non-Alcoholic Fatty Liver Disease Among Obstructive Sleep Apnea Patients: A Case-Control Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-6104","authenticated-orcid":false,"given":"Rana","family":"Toghan","sequence":"first","affiliation":[{"name":"Medical Physiology Department, Faculty of Medicine, Qena University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7006-8866","authenticated-orcid":false,"given":"Tarek A.","family":"Salem","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Qassim University, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1643-7437","authenticated-orcid":false,"given":"Eptehal","family":"Dongol","sequence":"additional","affiliation":[{"name":"Chest Diseases Department, Faculty of Medicine, Qena University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2680-6913","authenticated-orcid":false,"given":"Fatma Rabea A.","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Faculty of Medicine, Qena University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0719-6930","authenticated-orcid":false,"given":"Omyma Galal","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahlam Mohammed Sabra","family":"Ali","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Faculty of Medicine, Qena University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2698-9438","authenticated-orcid":false,"given":"Mohammed H.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Qena University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Abdelhady","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Luxor University, Luxor 85951, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3045-2716","authenticated-orcid":false,"given":"Rehab H.","family":"Abdel-Aziz","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Faculty of Medicine, Qena University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.drudis.2021.11.001","article-title":"Obesity and insulin resistance: Pathophysiology and treatment","volume":"27","author":"Tong","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000988","article-title":"Obstructive sleep apnea and cardiovascular disease: A scientific statement from the American Heart Association","volume":"144","author":"Yeghiazarians","year":"2021","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s11325-017-1576-4","article-title":"Prevalence of obstructive sleep apnea among obese toddlers and preschool children","volume":"22","author":"Katz","year":"2018","journal-title":"Sleep Breath."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1136\/gutjnl-2019-318813","article-title":"Epidemiology of chronic liver diseases in the USA in the past three decades","volume":"69","author":"Younossi","year":"2020","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.3748\/wjg.v26.i20.2669","article-title":"Association between non-alcoholic fatty liver disease and obstructive sleep apnea","volume":"26","author":"Umbro","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Tang, H., Lv, F., Zhang, P., Liu, J., and Mao, J. (2023). The impact of obstructive sleep apnea on nonalcoholic fatty liver disease. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1254459"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lee, J.-Y., Kim, C.-W., Lee, K.-C., Lee, J.-H., Kang, S.-H., Li, S.-W., Kim, K., and Hong, S.-J. (2021). Effect of intermittent hypoxia on metabolic syndrome and insulin resistance in the general male population. Medicina, 57.","DOI":"10.3390\/medicina57070668"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lavalle, S., Masiello, E., Iannella, G., Magliulo, G., Pace, A., Lechien, J.R., Calvo-Henriquez, C., Cocuzza, S., Parisi, F.M., and Favier, V. (2024). Unraveling the complexities of oxidative stress and inflammation biomarkers in obstructive sleep apnea syndrome: A comprehensive review. Antioxidants, 14.","DOI":"10.3390\/life14040425"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.32571\/ijct.1325830","article-title":"HIF-1\u03b1: A potential biomarker in obstructive sleep apnea","volume":"7","author":"Polat","year":"2023","journal-title":"Int. J. Chem. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16825","DOI":"10.1074\/jbc.R117.799973","article-title":"Oxygen availability and metabolic reprogramming in cancer","volume":"292","author":"Xie","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_11","unstructured":"Berry, R.B., Brooks, R., Gamaldo, C.E., Harding, S.M., Lloyd, R.M., Marcus, C.L., and Vaughn, B.V. (2015). The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications, Version 2.2, American Academy of Sleep Medicine. Available online: www.aasm.org."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"182","DOI":"10.4236\/ijcm.2020.114018","article-title":"Non-alcoholic fatty liver disease as a coronary heart disease severity predictor","volume":"11","author":"Ismael","year":"2020","journal-title":"Int. J. Clin. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1007\/s00125-017-4340-1","article-title":"Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: A population-based and inter-laboratory study","volume":"60","author":"Isokuortti","year":"2017","journal-title":"Diabetologia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41392-023-01496-3","article-title":"Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome","volume":"8","author":"Lv","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41392-022-01080-1","article-title":"Hypoxia signaling in human health and diseases: Implications and prospects for therapeutics","volume":"7","author":"Luo","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.5664\/jcsm.8682","article-title":"Patients with obstructive sleep apnea present with chronic upregulation of serum HIF-1\u03b1 protein","volume":"16","author":"Gabryelska","year":"2020","journal-title":"J. Clin. Sleep Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.chest.2018.09.030","article-title":"Sleep study and oximetry parameters for predicting postoperative complications in patients with OSA","volume":"155","author":"Suen","year":"2019","journal-title":"Chest"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5042","DOI":"10.1172\/JCI137560","article-title":"Hypoxia-inducible factors and obstructive sleep apnea","volume":"130","author":"Prabhakar","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41366-023-01257-w","article-title":"Obstructive sleep apnea is associated with impairment of beta-cell response to glucose in children and adolescents with obesity","volume":"47","author":"Umano","year":"2023","journal-title":"Int. J. Obes."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rodrigues, S., Bortolotto, L.A., Beyl, R.A., and Singh, P. (2023). Severity of sleep apnea impairs adipose tissue insulin sensitivity in individuals with obesity and newly diagnosed obstructive sleep apnea. Front. Sleep, 2.","DOI":"10.3389\/frsle.2023.1295301"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sobczak, A.I., Blindauer, C.A., and Stewart, A.J. (2019). Changes in plasma free fatty acids associated with type 2 diabetes. Nutrients, 11.","DOI":"10.3390\/nu11092022"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1007\/s11325-020-02018-z","article-title":"Obstructive sleep apnea and liver injury in severely obese patients with nonalcoholic fatty liver disease","volume":"24","author":"Zhang","year":"2020","journal-title":"Sleep Breath."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"917","DOI":"10.2147\/NSS.S468420","article-title":"Association of obstructive sleep apnea with nonalcoholic fatty liver disease: Evidence, mechanism, and treatment","volume":"16","author":"Wang","year":"2024","journal-title":"Nat. Sci. Sleep"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41581-022-00587-8","article-title":"The effect of HIF on metabolism and immunity","volume":"18","author":"Taylor","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00109-023-02308-5","article-title":"The role of hypoxia-inducible factor 1\u03b1 in hepatic lipid metabolism","volume":"101","author":"Luo","year":"2023","journal-title":"J. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1038\/s12276-023-01113-x","article-title":"Sensing the oxygen and temperature in adipose tissues\u2014Who\u2019s sensing what?","volume":"55","author":"Kang","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Foglia, B., Novo, E., Protopapa, F., Maggiora, M., Bocca, C., Cannito, S., and Parola, M. (2021). Hypoxia, hypoxia-inducible factors and liver fibrosis. Cells, 10.","DOI":"10.3390\/cells10071764"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1097\/MCP.0000000000001122","article-title":"Hypoxic burden\u2014Definitions, pathophysiological concepts, methods of evaluation, and clinical relevance","volume":"30","author":"Parekh","year":"2024","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.4254\/wjh.v13.i11.1688","article-title":"Abnormal liver enzymes: A review for clinicians","volume":"13","author":"Kalas","year":"2021","journal-title":"World J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xuan, Y., Wu, D., Zhang, Q., Yu, Z., Yu, J., and Zhou, D. (2024). Elevated ALT\/AST ratio as a marker for NAFLD risk and severity: Insights from a cross-sectional analysis in the United States. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1457598"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/4861\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:01:21Z","timestamp":1782273681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/4861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":30,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15134861"],"URL":"https:\/\/doi.org\/10.3390\/jcm15134861","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}