Chronic intermittent hypoxia contributes to non-alcoholic steatohepatitis progression in patients with obesity

Hepatol Int. 2022 Aug;16(4):824-834. doi: 10.1007/s12072-022-10347-2. Epub 2022 Jun 6.

Abstract

Background and purpose: The association between the severity of obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in patients with obesity remains unclear. We conducted this study to determine the effects of OSA on the severity of NAFLD in individuals with obesity and its link to the development of non-alcoholic steatohepatitis (NASH).

Methods: Patients were subjected to standard polysomnography up to 1 week before undergoing bariatric surgery, during which liver biopsy specimens were obtained. The apnea-hypopnea index (AHI) obtained by polysomnography was used to determine the severity of OSA.

Results: In total, 183 patients with obesity and biopsy-confirmed NAFLD were included; 49 (27%) had NASH. Patients with NASH had higher AHIs (p = 0.014) and oxygen desaturation indices (p = 0.031), more frequent OSA (p = 0.001), and lower minimum oxygen saturation (p = 0.035). The severity of OSA was directly correlated with the NAFLD activity score (p < 0.001), NASH activity grade (p < 0.001), semi-quantitative indices of lobular inflammation (p = 0.001), and hepatocyte ballooning (p = 0.006). The odds ratios (95% confidence intervals) for NASH and severe NASH (activity grade ≥ 3) associated with moderate-to-severe OSA were 3.85 (1.35-10.94; p < 0.05) and 5.02 (1.66-15.18; p < 0.01), respectively, after adjusting for sex, age, body mass index, waist circumference, insulin resistance values, and metabolic syndrome.

Conclusions: Chronic intermittent hypoxia caused by OSA may aggravate NAFLD and lead to a higher risk of NASH in patients with obesity.

Keywords: Apnea–hypopnea index; Chronic intermittent hypoxia; Liver biopsy; Non-alcoholic fatty liver disease; Non-alcoholic fatty liver disease activity score; Non-alcoholic steatohepatitis; Non-alcoholic steatohepatitis activity grade; Obesity; Obstructive sleep apnea; Polysomnography.

MeSH terms

  • Humans
  • Hypoxia / complications
  • Non-alcoholic Fatty Liver Disease* / complications
  • Obesity / complications
  • Polysomnography / adverse effects
  • Sleep Apnea, Obstructive* / complications
  • Sleep Apnea, Obstructive* / pathology