OSAS‐Related Inflammatory Mechanisms of Liver Injury in Nonalcoholic Fatty Liver Disease

Abstract

Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors. OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population. Several studies suggest that the chronic intermittent hypoxia (CIH) of OSAS patients may per se trigger liver injury, inflammation, and fibrogenesis, promoting NAFLD development and the progression from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells. In this review, we focus on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor (HIF), nuclear factor kappa B (NF-κB), YKL-40, unfolded protein response, and hypoxic adipose tissue inflammation, which all could provide novel potential therapeutic approaches for the management of NAFLD patients with OSAS.

Association between self-reported snoring and arterial stiffness: data from the Brisighella Heart Study

“…Finally, the finding that at the baseline snorers (with or without apnoea) are significantly older and more overweight than non-snorers, and have higher level of FPG, ALT and Gamma-GT, while lower HDL-cholesterolemia, is in line with previous data that also find OSAS patients more frequently affected by the metabolic syndrome and non-alcoholic fatty liver disease [44].…”

Non-alcoholic fatty liver disease: An expanded review

“…A budding association of OSA with diabetes mellitus, metabolic syndrome, and cardiovascular disease has started to appear in the last few years[41]. In the general population, obstructive sleep apnea has a prevalence of around 4% with that number jumping to 35%-45% in obese individuals[15].…”

Macrophage‐Specific Hypoxia‐Inducible Factor‐1α Contributes to Impaired Autophagic Flux in Nonalcoholic Steatohepatitis

“…In patients with metabolic syndrome, NAFLD evolves from steatosis to nonalcoholic steatohepatitis (NASH) and ultimately to cirrhosis . The clinical comorbidities of NAFLD/NASH include obesity, insulin resistance, and obstructive sleep apnea leading to periodic hypoxia . Recent studies demonstrate that hypoxia promotes liver triglyceride accumulation, necroinflammation, and fibrosis during NAFLD .…”