Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway during sleep leading to intermittent
hypoxia (IH). OSA has been associated with all components of the
metabolic syndrome as well as with
non-alcoholic fatty liver disease (
NAFLD).
NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to
steatohepatitis (NASH),
liver fibrosis, and
cirrhosis. The gold standard for the diagnosis and staging of
NAFLD is liver biopsy.
Obesity and
insulin resistance lead to
liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of
NAFLD on liver biopsy. However, neither prospective nor interventional studies with
continuous positive airway pressure treatment have been performed. Studies in a mouse model showed that IH causes
triglyceride accumulation in the liver and liver injury as well as hepatic
inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1) IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing
free fatty acids (FFA) flux into the liver; (2) IH up-regulates
lipid biosynthetic pathways in the liver; (3) IH induces oxidative stress in the liver; (4) IH up-regulates
hypoxia inducible factor 1 alpha and possibly
HIF-2 alpha, which may increase hepatic steatosis and induce liver
inflammation and
fibrosis. However, the role of FFA and different
transcription factors in the pathogenesis of IH-induced
NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of
NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done.