July 1, 2008 A fatty liver disease that is not well-known in overweight and obese children may be a precursor of cardiovascular disease, researchers reported in Circulation: Journal of the American Heart Association.
Researchers performed a case-controlled study of 150 overweight children with biopsy-proven non-alcoholic fatty liver disease (NAFLD) and 150 overweight children without NAFLD. Participants were well matched in age (average 12.7 years), sex and severity of obesity. More than half of the children in each group were in the 99th percentile for body mass index.
The overweight children with NAFLD had significant cardiovascular risk including higher levels of fasting glucose, insulin, total cholesterol, low-density lipoprotein (LDL, "bad" cholesterol), triglycerides and higher systolic and diastolic blood pressure than the control group. The children with NAFLD also had significantly lower levels of high-density lipoprotein (HDL, "good" cholesterol) than the control group.
Researchers found the distribution of the disease by race and ethnicity was also significantly different, with more Hispanic and Asian children in the fatty liver group and more white and black children in the control group. They also found that children with metabolic syndrome were five times more likely to have NAFLD as overweight and obese children without metabolic syndrome.
"Our results demonstrate that obese children and adolescents with a definitive diagnosis of NAFLD have a more severe cardiovascular risk profile than their age, sex and BMI-matched peers," said Jeffrey Schwimmer, M.D., lead author of the study and associate professor of pediatrics at the University of California, San Diego. "These collective data illustrate that fat accumulation in the liver may play a more important role than obesity itself in determining the risk for 'weight-related' metabolic co-morbidities. Thus, in children and adolescents, NAFLD may serve as a marker to stratify the cardiovascular risk of overweight and obese patients."
NAFLD is the most common cause of liver disease in children and is associated with metabolic syndrome, a clustering of risk factors for the development of cardiovascular disease and type 2 diabetes. NAFLD is characterized by the presence of oily droplets of triglycerides in liver cells. More than 6 million children in the United States are affected.
Strengths of the study included the large series of biopsy-proven pediatric NAFLD and the use of a well-matched control group, said Schwimmer, who is also director of the Fatty Liver Clinic at Rady Children's Hospital San Diego.
Other observations include:
- NAFLD in overweight children is strongly associated with metabolic syndrome. The association is independent of both body mass index and insulin sensitivity.
- All study children were overweight, with 96 percent classified as obese.
- More than half of the subjects in each group (NAFLD 57 percent, controls 54 percent) had a BMI 99th percentile.
Fatty liver disease often has no outward symptoms, which contributes to it going undetected. Although some children will have symptoms such as abdominal pain or fatigue, the majority remain symptom-free until the disease is in very advanced stages. Long-term studies are ongoing to determine the causes and consequences of fatty liver disease, researchers said.
"Roughly 25 percent of children with fatty liver will develop hepatitis as children or by their 20s," Schwimmer said. "Of these, approximately 20 percent may go on to develop cirrhosis as young adults, with a subsequent life expectancy of seven years.
"Overweight children age 8 or older and especially those with symptoms of metabolic syndrome should be screened for NAFLD," Schwimmer said. "I think many parents have not ever heard of NAFLD, and many physicians are not aware of its prevalence and severity in children. Identification of NAFLD in a child should prompt counseling that addresses nutrition, physical activity and avoidance of smoking."
Co-authors are: Perrie E. Pardee, B.S.; Joel E. Lavine, M.D., Ph.D.; Aaron K. Blumkin, M.S.; and Stephen Cook, M.D.
The study was partially funded by the Rest Haven Foundation; the National Institute of Diabetes, Digestive and Kidney Diseases; the National Center for Research Resources of the National Institutes of Health for the General Clinical Research Center at UCSD; and the National Heart, Lung, and Blood Institute.
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