A group of French doctors claims people with sleep apnea have a higher risk of contracting non-alcoholic fatty liver disease (NAFLD), regardless of whether they're obese or not. Their research findings are published in the June issue of the journal Hepatology.¹

Breathing Difficulties During Sleep
It's estimated that up to 4 percent of those in the general population have obstructive sleep apnea, according to study investigators Lawrence Serfaty, MD, a hepatologist at Saint-Antoine Hospital in Paris, and his associates. In those with the condition, breathing simply stops during sleep, sometimes hundreds of times during the night. As a result, people suffer from excessive daytime sleepiness and complain of poor qualities of life. Obstructive sleep apnea is actually one type of the disorder, in which the airway is obstructed due to some mechanical blockage. The other type, known as central sleep apnea, involves a malfunction in the brain's normal signal to breathe.²

Symptoms of sleep apnea may include restless sleep; loud, heavy snoring; falling asleep during daytime activities; morning headaches; loss of energy; trouble concentrating; irritability; and forgetfulness.²

Since people with this disorder are often obese, they also face the risk of contracting non-alcoholic fatty liver disease, characterized by accumulation of fat in the liver's cells and caused by factors other than consuming alcohol. These factors might include extreme weight gain, diabetes, certain related illnesses, or certain drugs. NAFLD may lead to non-alcoholic steatohepatitis (NASH), a disease diagnosed when the fat in the liver leads to inflammation and damage to its cells.³

Liver Disease Link?
While previous research has hinted that obstructive sleep apnea could be an independent risk factor for liver disease, there hasn't been much reported on whether there's a direct link between sleep apnea and fatty liver disease, regardless of whether a person is obese or not, the study investigators noted.

To determine whether there's such an association and identify the possible mechanism involved, the study authors recruited 163 patients who had been referred to the Sleep Unit at Saint-Antoine Hospital to undergo evaluations for obstructive sleep apnea. Each person's age, sex, weight, history of diabetes, hypertriglycerides, and blood pressure were recorded. Each was also asked about his or her history of alcohol consumption.

In the morning immediately after sleep, blood samples were taken and tested for the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT). These enzymes are released into the bloodstream by the liver when it is damaged. As such, physicians use the enzyme levels as indicators of liver disease.⁴

Patients with elevated enzymes then underwent liver biopsies—also performed in the morning—to confirm the findings. Liver diseases other than fatty liver disease were excluded from the study.

In 44 people, obstructive sleep apnea was severe. It was moderate in 84 patients, and absent in 35 of them. The latter group was used as a control, or comparison, group to the patients with sleep apnea. Those with the severe sleep apnea were more commonly male, were more overweight or obese, and were more likely to have diabetes or high blood pressure compared to those without the condition.

Liver enzymes were also more often significantly higher in those with severe obstructive sleep apnea, Serfaty and his colleagues found. Enzymes were higher in about one-third of the patients with severe sleep apnea, compared to under 20 percent of those with moderate sleep apnea, and just 8 percent of those without sleep apnea. Factors significantly associated with high liver enzymes included not only severe obstructive sleep apnea, but also higher weight, Serfaty and his team noted.

In all, 32 patients had elevated liver enzymes, and liver biopsies were performed in about half of them to verify the association between liver disease and sleep apnea. Of those, nine had severe obstructive sleep apnea, six had moderate sleep apnea, and three patients had none. Most of these patients with obstructive sleep apnea also had NASH and/or fibrosis, two signs of liver disease, regardless of whether or not they were obese, which in itself is a risk factor for fatty liver disease.

The researchers also measured levels of insulin resistance in the patients with severe obstructive sleep apnea, and found they were more likely to have this condition.

In conclusion, they found that patients with more advanced steatosis, necrosis, and fibrosis in their livers also had severe obstructive sleep apnea. "This study shows that severe obstructive sleep apnea is a risk factor for abnormal liver enzymes and steatohepatitis independent of overweight states," wrote Serfaty's group.

Investigating the Causes
What's the underlying reason for the link between sleep apnea and liver disease? Increased insulin resistance in these patients is likely one cause of the liver injury, they stated. That's because insulin resistance can lead to increased levels of free fatty acids in the liver, the so-called "first hit" in nonalcoholic fatty liver disease, the investigators stated. But it's believed sleep apnea caused the insulin resistance independent of obesity, based on the findings of other studies.

It could also be speculated that the obesity of the patients is the link. However, in this study, the risk of liver disease was greater, regardless of obesity, the investigators pointed out.

There was one caveat. "Considering the limited number of patients with liver biopsy, the results must be considered with caution," Serfaty's team wrote.

In the meantime, further clinical studies are needed, they wrote, to determine whether treating obstructive sleep apnea might improve liver disease.

1. Tanne F, Gagnadoux F, Chazouilleres O et al. Chronic liver injury during obstructive sleep apnea. Hepatology 2005 Jun;41(6):1290-6.
2. National Institute of Neurological Disorders and Stroke. National Institutes of Health. NINDS Sleep Apnea Information Page. Available at: http://www.ninds.nih.gov/disorders/sleep_apnea/sleep_apnea.htm. Accessed June 9, 2005.
3. American Liver Foundation. What is NAFLD/NASH? Available at: http://www.liverfoundation.org/cgi-bin/dbs/articles.cgi?db=articles&uid=default&ID=1027&view_records=1. Accessed June 9, 2005.
4. Merck Manual. Liver Function Tests. Available at: http://www.merck.com/mmhe/sec10/ch134/ch134a.html. Accessed June 9, 2005.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.