Role of Hypoxia-Inducible Factor-1α in the Pathophysiology of Non-Alcoholic Fatty Liver Disease Among Obstructive Sleep Apnea Patients: A Case-Control Study.

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-α (HIF-1α) 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-16 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-α, fasting blood glucose, and fasting insulin were measured.

Results

HIF-1α 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 < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) mean score (3.92 vs. 1.21, p < 0.0001), HIF-1α level (6.01 vs. 2.14 ng/L, p = 0.045), and the LSM score (5.55 vs. 3.85 kPa, p < 0.001). HIF-1α showed significant positive correlations with AHI (r = 0.515, p < 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-1α levels were significantly higher in OSA patients with NAFLD and correlated with indices of hepatic steatosis, HIF-1α 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.