Pediatric nonalcoholic fatty liver boosts cardiovascular risk.

COLORADO SPRINGS -- Pediatric nonalcoholic fatty liver disease is strongly associated with multiple cardiovascular risk factors, often in excess of clinical thresholds for considering pharmacotherapy, Dr. Stephen Cook said at a conference of the American Heart Association.

Moreover, the prevalence of metabolic syndrome in children and adolescents with nonalcoholic fatty liver disease (NAFLD) is twice that seen in equally obese youths without the hepatic disease, according to Dr. Cook, a pediatrician at the University of Rochester (N.Y.) Medical Center.

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He added that these new findings from a 300-patient case-control study underscore the importance of routine screening for NAFLD in obese youth as recently recommended by an expert panel comprising representatives of 15 professional organizations (Pediatrics 2007;120:S163-288).

"This is a really important problem," Dr. Cook said in an interview. "The pediatric GI community sees NAFLD as a severe precursor which, if not reversed, is going to be one of the leading causes of liver failure in adulthood."

In addition, the cardiovascular risk profiles documented in this study are disturbing. They raise the prospect that youths with NAFLD may be predisposed to highly premature cardiovascular morbidity and mortality, he noted.

Dr. Cook reported on 150 severely obese children and adolescents with biopsy-proven NAFLD and an equal number of age-, gender-, and obesity-matched controls with normal liver function tests and no hepatomegaly or other signs of NAFLD.

"Across the board, these obese kids with fatty liver had far higher triglycetides, LDL, fasting blood glucose, insulin, blood pressure, and lower HDL than matched controls who were just as obese," Dr. Cook said.

A total of 80 youths with NAFLD met the three-component definition for metabolic syndrome, compared with 35 controls.

In a logistic regression analysis controlled for age, race, gender, insulin resistance, and body mass index, subjects with NAFLD were two- to sixfold more likely than were controls to exceed treatable thresholds for various cardiovascular risk factors (see graphic).

The recent expert panel recommendations included comprehensive reports on the treatment, prevention, and assessment of pediatric obesity. Panelists recommended that lipid profiles routinely be obtained in youths who are at or above the 85th percentile for BMI, and recommended liver function tests, fasting blood glucose, and lipid profiles in all those at or above the 95th percentile.

Although liver biopsy is required for definitive diagnosis of NAFLD, there is considerable interest in noninvasive screening. Magnetic resonance imaging is probably the best method at present, followed by CT with contrast. Ultrasound is the least informative imaging method; however, fatty infiltration does cause the liver to light up on ultrasound and the attenuation can be compared with the spleen, Dr. Cook said.

Dr. Jeffrey B. Schwimmer of the University of California, San Diego, is lead investigator on this ongoing pediattic NAFLD research project and was part of the expert panel.

BY BRUCE JANCIN

Denver Bureau Odds Ratios for Cardiovascular Risk Factors In Pediatric Nonalcoholic Fatty Liver Disease LDL 6.0 [greater than or equal to] 4.14 mmol/L Fasting blood 5.8 glucose >5.6 mmol/L Triglycerides 4.9 [greater than or equal to] 1.68 mmol/L Blood pressure 2.1 [greater than or equal to] 95th percentile Control group (n = 150) Notes: Based on data for 150 severely obese children and adolescents with biopsy-proven NAFLD. Odds ratios adjusted for age, race, gender, insulin resistance, and body mass index. Source: Dr. Cook Note: Table made from bar graph.