Researchers from Johns Hopkins Bayview Medical Center Bariatric Surgery Clinic have found that the chronic intermittent hypoxia that often characterizes Obstructive Sleep Apnea, a common form of SDB, is independently linked to the progression of liver disease.

In this study, researchers recruited 90 severely obese patients presenting for bariatric surgery at without known diagnoses of obstructive sleep apnea. Each patient underwent a sleep study and blood tests for markers of liver function, insulin resistance, and systemic inflammation. And, because standard practice for patients undergoing bariatric surgery is to biopsy the liver, the researchers were able to analyze liver tissue for signs of disease and link it to the severity and type of sleep disordered breathing they observed during the sleep study.

The results validated the link between Obstructive Sleep Apnea and insulin resistance, and further linked it to the level of hypoxemia experienced during the night versus simply the number of apneic events. Strikingly, of the patients whose liver tissue was analyzed, those who were observed to have severe nocturnal hypoxemia also exhibited "ballooning" of their hepatocytes and a pericellular fibrosis of the liver, indicating liver injury.

"We demonstrated that the severity of nocturnal oxyhemoglobin desaturation predicted the severity of insulin resistance and might be implicated in the development of liver disease. In contrast, severe obesity was associated with high levels of serum c-reactive protein (CRP), indicating systemic inflammation," said lead researcher, Vsevolod Y. Polotsky, M.D., Ph.D., of Johns Hopkins' Asthma and Allergy Center. "Interestingly, there was no relationship between the severity of nocturnal hypoxemia and serum CRP. This suggests that that obesity and Obstructive Sleep Apnea have distinct metabolic, inflammatory and hepatic profiles, which act in different detrimental ways on the liver."

"We hypothesize that severe obesity per se acts as a 'first hit' in the progression of liver disease, inducing hepatic steatosis, whereas the presence of the chronic intermittent hypoxemia that often characterizes Obstructive Sleep Apnea acts as a 'second hit'. The hypoxic stress of Obstructive Sleep Apnea may induce oxidative stress in the livers of patients with severe obesity, leading to further inflammation."

The clinical implications of the findings are clear: obesity and obstructive sleep apnea exert separate and perhaps additive negative effects on insulin resistance and the liver, and each disorder must be treated concomitantly in order to address the secondary complications.

"Our data suggest that patients with Obstructive Sleep Apnea and severe nocturnal hypoxemia should be screened for liver disease and, conversely, patients with liver disease should be screened for Obstructive Sleep Apnea," said Dr. Polotsky.

"We have developed a mouse model of intermittent hypoxia and have demonstrated that a combination of a high-fat diet and intermittent hypoxia leads to liver disease in those mice. We plan on continuing to use the model in future research. We plan to examine whether treatment of Obstructive Sleep Apnea with continuous positive airway pressure can improve or reverse liver disease."

This news briefing is based on an article published in the American Thoracic Society's peer-reviewed journal, the American Journal of Respiratory and Critical Care Medicine.

About the ATS

Founded in 1905, the American Thoracic Society is the world's leading medical association dedicated to advancing pulmonary, critical care and sleep medicine. The Society has more than 15,000 members who prevent and fight respiratory disease around the globe, through research, education, patient care and advocacy.

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