Table 1.
Human studies assessing the correlation between obstructive sleep apnea and nonalcoholic fatty liver disease
| Reference | Type of Study (Subject Population [n]); Country | NAFLD Assessment | OSA Diagnosis | Important Findings |
|---|---|---|---|---|
| Tanne et al,36 2005 | PSG (163); France | LFT or liver biopsy | PSG | Severe OSA is associated with elevation of liver enzymes, insulin resistance, and steatohepatitis. |
| Kallwitz et al,37 2007 | Bariatric surgery (85); USA | Liver biopsy | PSG (AHI ≥15/h) | OSA was associated with elevated ALT levels and a trend toward histologic evidence of progressive liver disease (inflammation and fibrosis). |
| Polotsky et al,18 2009 | Bariatric surgery (90); USA | LFT or liver biopsy | PSG | Oxygen desaturation >4.6% was associated with 1.5-fold increase in insulin resistance. Significant desaturations may predispose to steatohepatitis. |
| Daltro et al,15 2010 | Bariatric surgery (40); Brazil | Liver biopsy | PSG | OSA (AHI ≥15/h) was associated with insulin resistance but not with the severity of NASH. |
| Aron-Wisnewsky et al,8 2012 | Bariatric surgery (101); France | Liver biopsy | ODI by nocturnal oximetry | CIH was independently associated with hepatic fibrosis, fibroinflammation, and NAFLD activity score. |
| Turkay et al,27 2012 | PSG (71); Turkey | LFT, ultrasound | PSG | AHI, ODI, lowest desaturation values, and percentage of sleep duration with SpO2 <90% were independent predictors of NAFLD. |
| Corey et al,38 2013 | Bariatric surgery (159); USA | Liver biopsy | Electronic medical record | Absence of OSA was associated with normal liver histology in subjects undergoing bariatric surgery. |
| Mir et al,39 2013 | Population-based study, NHANES database. (NAFLD cases = 1572, controls = 8969); USA | LFT | Sleep Disorders Questionnaire | NAFLD was associated with sleep apnea (OR = 1.39, 0.98–1.97) |
| Minville et al,40 2014 | PSG (226); France | SteatoTest, Nash Test, and FibroTest | PSG | On multivariate analysis, nocturnal cumulative time spent at <90% of oxygen saturation was associated with hepatic steatosis but not with NASH. |
| Sundaram et al,41 2014 | Obese children aged 10–18 y (25); USA | Liver biopsy or LFT | PSG | Severity of hypoxemia and OSA were associated with transaminitis and advanced liver histology. |
| Nobili et al,17 2014 | Children with NAFLD undergoing PSG (65); Italy | LFT or liver biopsy | PSG | Severity of OSA was independently associated with presence of NASH, significant fibrosis, and NAFLD activity score. |
| Lin et al,42 2015 | NAFLD subjects undergoing sleep apnea assessment (85); China | Ultrasound | PSG | ODI and average O2 saturation were independently associated with elevated ALT and AST, respectively. |
| Agrawal et al,43 2015 | Subjects from liver clinic with NAFLD and chest clinic with OSA (123); India | Ultrasound, Fibroscan |
PSG | OSA severity was an independent predictor of significant hepatic fibrosis in NAFLD subjects. |
| Corey et al,14 2015 | Bariatric surgery (213); USA | Liver biopsy | PSG | OSA was independently associated with transaminitis, NASH, and advanced liver histology. |
| Alkhouri et al,44 2015 | Obese children evaluated for OSA (58); USA | Circulating markers of hepatic apoptosis or inflammation | PSG | Circulating markers of apoptosis and macrophage activation were significantly increased in obese children with OSA. Treatment reduced markers of macrophage activation. |
| Petta et al,45 2015 | NAFLD subjects with elevated ALT, undergoing OSA assessment (126); Italy | LFT, liver biopsy | Cardiorespiratory polygraph |
Prevalence of OSA was higher in subjects with F2–F4 fibrosis. Significant fibrosis was associated with nocturnal oxygen saturation (SaO2) <95%. |
| Cakmak et al,46 2015 | NAFLD subject undergoing OSA assessment (137); Turkey | Ultrasound | PSG | AHI and ODI were significantly higher in subjects with moderate and severe NAFLD. A strong association was noted between reduction in lowest O2 saturation and increase in NAFLD severity. |
| Benotti et al,13 2016 | Bariatric surgery (362); USA | Liver biopsy | PSG | Severity of OSA was associated with NAFLD liver histology. |
| Qi et al,47 2016 | Nonobese subjects undergoing PSG and abdominal ultrasound (175); China | Ultrasound | PSG | In nonobese subjects, lowest oxygen saturation was independently associated with NAFLD. |
| Trzepizur et al,19 2016 | Multisite cross-sectional study (1285); France | Hepatic steatosis index, LFT, FibroMeter | PSG or home sleep test | Risk of hepatic steatosis increased with severity of OSA and sleep-related hypoxemia. |
| Asfari et al,48 2017 | Cross-sectional study using NIS database (OSA subjects = 1490150, non-OSA = 29,222 374); USA | ICD-9-CM | ICD-9-CM | OSA subjects were 3 times more likely to have NASH compared with subjects without OSA. |
| Ding et al,49 2018 | Subjects with suspected apnea undergoing OSA and NAFLD assessment (415); China | LFT and ultrasound | PSG | Percentage of total sleep time spent with oxygen saturation of <90%, lowest oxygen saturation, and insulin resistance were associated with NAFLD. |
Abbreviations: ICD-9-CM, international classification of diseases, ninth revision, clinical modification; LFT, liver function test; NHANES, National Health And Nutrition Examination Survey; NIS, national inpatient sample; ODI, oxygen desaturation index; PSG, polysomnography.