ATLANTA — Obese children are at risk for developing nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, which can lead to fibrosis and cirrhosis, speakers said at a meeting sponsored by the American Association for the Study of Liver Diseases.
A significant number of children are probably affected by nonalcoholic fatty liver disease (NAFLD), according to Dr. Jeffrey B. Schwimmer, a pediatrician at the University of California, San Diego. Various studies have indicated that between 10% and 77% of obese children in China, Italy, Japan, and the United States have NAFLD. An estimated 5%–10% of those children have advanced fibrosis at the time of diagnosis. Demographic factors influence prevalence: boys and Hispanic children are more likely to have NAFLD than are girls and black children.
The first detectable sign of NAFLD is often an elevated serum alanine aminotransferase level. However, diagnosis can be challenging, because children often are asymptomatic, but may have NAFLD and even nonalcoholic steatohepatitis (NASH), despite having normal alanine aminotransferase levels. No single blood test can indicate NAFLD; biopsy is the definitive diagnostic tool for both NAFLD and NASH.
Dr. Philip Rosenthal, professor of pediatrics at the University of California, San Francisco, emphasized the importance of a histologic examination for determining the extent of disease and for distinguishing between simple steatosis and steatohepatitis. Steatohepatitis and fibrosis are commonly observed in children with NASH who are undergoing biopsy, and cirrhosis with rapid progression has been observed.
Dr. Rosenthal also recommended that clinicians look for signs of portal hypertension, including gastrointestinal bleeding and ascites.
Treatments for pediatric NASH have not been evaluated in controlled trials with long follow-up periods. Current treatments primarily aim to reduce steatosis and associated disorders. Prevention and treatment of metabolic syndrome through diet and exercise, insulin-sensitizing agents, and lipid-lowering drugs are central treatment strategies. Metformin may be beneficial in these patients, as it appears to improve NASH in nondiabetic pediatric patients.
Treatment of Nonalcoholic Fatty Liver Disease (TONIC), a randomized, phase III trial sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, will be evaluating metformin and vitamin E in children with NAFLD/NASH.
Reducing body weight also remains a primary goal in treating pediatric NAFLD, according to Dr. Paul B. Pencharz, professor of pediatrics at the University of Toronto in Ontario.
“With rare exception,” he noted, “NAFLD is associated with excess body fat. In combination with diet, exercise increases loss of weight and excess body fat. As body weight decreases, glucose tolerance improves and, hence, NAFLD would be expected to be improved as well.”
Dr. Pencharz emphasized family involvement as the primary factor for changing behaviors, because “If the family won't buy in, you cannot change the lifestyle.”
In addition to diet and exercise, indirect approaches to weight control may be useful. Two drugs are available for children, although they have only been evaluated in adolescents. They are orlistat, the pancreatic lipase inhibitor; and sibutramine, which alters appetite control by inhibiting uptake of 5-hydroxytryptamine (serotonin) and norepinephrine.
Gastric reduction also is beginning to be evaluated in adolescents. This surgical approach may be beneficial in certain patients; compliance is crucial, particularly in the few months after surgery.