Children's Hospital Colorado

Non-Alcoholic Fatty Liver Disease

Digestive Health | December 01, 2016


For families

  • NAFLD is becoming more common in children.
  • Our researchers found that poor breathing during sleep can worsen NAFLD.
  • We are conducting new research to determine if treating poor breathing in patients with NAFLD will prevent the disease from progressing.

For health professionals

  • Our researchers sought to better understand the effect of OSA on patients with NAFLD.
  • They studied patients with and without NAFLD to determine the relationship of OSA to NAFLD, OSA with oxidative stress, oxidative stress with liver histology, and antioxidants to NAFLD and lipid peroxidation.
  • They found that sleep-disordered breathing in patients with NAFLD is a key trigger of oxidative stress, which promotes the progression of pediatric nonalcoholic steatohepatitis.

Background

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and the most common disease seen in the Pediatric Liver Center  at Children’s Hospital Colorado’s Digestive Health Institute.

Previously considered an adult disease, NAFLD now widely impacts children— and its occurrence has been increasing in younger ages. While the rise in NAFLD has seemingly gone hand-in-hand with the growing pediatric obesity epidemic, not all children who are obese suffer from NAFLD and not all children with NAFLD are obese.

Patients with NAFLD are at risk for obstructive sleep apnea (OSA) and chronic intermittent nocturnal hypoxia. Poor breathing leads to poor oxygenation, and hypoxia and ischemia can increase liver damage. This concept led principal investigator Dr. Shikha Sundaram and other researchers in our Digestive Health Institute to wonder, “What does OSA do to patients with non-alcoholic fatty liver disease?”

Methods

Between June 2009 and January 2014, researchers in the Digestive Health Institute studied pediatric patients ages 8 to 18 years old with confirmed NAFLD after liver biopsy. Lean age-matched control subjects with no liver disease were also enrolled. NAFLD subjects had significantly elevated aminotransferases, inflammatory markers and evidence of the metabolic syndrome compared to the lean controls.

Researchers then studied the following:

  • Relationship of OSA/hypoxia to NAFLD
  • Relationship of OSA/hypoxia with oxidative stress
  • Relationship of oxidative stress with liver histology
  • Relationship of antioxidants to NAFLD and lipid peroxidation
Infographic about NAFLD study participants: 36 obese subjects with confirmed NAFLD, 14 lean controls, 25 NAFLD patients met study criteria for OSA and/or nocturnal hypoxia.

Results

Key findings included:

  • OSA/hypoxia is common in pediatric NAFLD
  • NASH patients experience more severe OSA and hypoxia than those without NASH
  • More severe OSA/hypoxia is associated with elevated aminotransferases, hepatic steatosis, inflammation, NASH and fibrosis
  • Higher blood hematocrit levels are associated with more severe hepatic fibrosis
  • OSA/nocturnal hypoxia triggers oxidative stress and injury, promoting the progression of pediatric NASH
Graphic shows 30 million people have non-alcohol fatty liver disease, 8.6 million have NASH, 1% of 2-4 year olds have NAFLD, 17% of 15-19 year olds have NAFLD, 38% of obese children have NAFLD.

Conclusion

Study data show sleep-disordered breathing is an important trigger of oxidative stress that promotes the progression of pediatric NAFLD to NASH. Further studies are being conducted to demonstrate if effective treatment of OSA and nocturnal hypoxia in obese patients will prevent or reverse NASH.

Close-up of a young boy sleeping.

How to refer a patient

The Pediatric Liver Center team welcomes consultations and can be reached at 720-777-6669. The center offers specialized staff for weight loss training and counseling, understanding of and evaluation of co-morbidities and novel treatments and clinical trials



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