Government scientists are about to take a hard look at the underlying origins of non-alcoholic steatohepatitis, or NASH, in children. It's a clinical trial just getting underway, sponsored by the NASH Clinical Research Network at the National Institutes of Health (NIH). The network oversees clinical trials, and is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

An earlier study, launched in early 2005, is focusing on adults with the disease.

Testing Therapies for Pediatric NAFLD
The so-called Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC) Trial, is enrolling 180 boys and girls between the ages of eight and 15 with nonalcoholic fatty liver disease (NAFLD). "As the first randomized, controlled trial for children with NAFLD, TONIC provides researchers a platform to conduct rigorous studies on how safe and effective vitamin E and metformin are in treating children with this liver disease," explained Patricia Robuck, PhD, MPH, a project scientist with the NASH Clinical Research Network and director of the Clinical Trials Program at the NIDDK.

The children taking part in the study will receive doses of vitamin E or metformin, a drug prescribed for people diagnosed with a condition characterized by insulin resistance, or a placebo. The trial is expected to last for more than two years. While there are no weight restrictions in the study, most of the children to be enrolled are expected to be obese, officials stated, and the volunteers will need an initial biopsy that confirms the presence of NAFLD to be eligible to take part in the research.

Fatty Liver Disease v NASH
Nonalcoholic fatty liver disease is characterized by the accumulation of fat in the liver cells. While this fat doesn't normally damage the liver, if it progresses to NASH, it can be potentially destructive. NASH, similarly, is characterized by fatty liver, but it causes serious inflammation, as well. This can, in turn, damage the liver cells.

While there is no known specific cause of NASH, experts do know that it is not connected to other causes of chronic liver disease like hepatitis, autoimmune disorders, alcohol or drug toxicities.¹

NASH typically occurs in overweight, middle-aged, and often diabetic people who abstain from alcohol.1 It can result from nonalcoholic fatty liver disease, which is what occurs most often in children, though adults can also be diagnosed with NAFLD.

According to experts, while there seems to be a link between fatty liver disease and obesity, scientists have not been able to establish that obesity causes NAFLD.² In this latest trial, however, investigators hope to learn more about what causes the disease in children.

Fatty Liver Disease in Children
Pediatric NAFLD is becoming a trend in the United States, according to the NIH. Once considered a disease exclusive to adults over age 40, it now is becoming increasingly common in children. But experts say pinning down the exact prevalence of NAFLD is difficult due to several factors, such as the age group being examined, the racial/ethnic background of the patients, and the methods used to evaluate the existence of fatty liver.³ The latter includes magnetic resonance imaging (MRI), ultrasound, and blood tests to look for levels of liver enzymes, which indicate liver damage.

Medical experts are concerned that if the disease becomes common in children, it will increase their risk of developing cirrhosis, liver failure, and death, similar to the risks that adults face. Studies found that boys more often than girls, and Hispanics more than other ethnic groups, face a higher risk of contracting NAFLD.³

"The rise in the rates of NAFLD in children likely mirrors the increase in obesity, making it the most prevalent liver disease in American children today," explained Joel Lavine, MD, PhD, chair of the NASH-Clinical Research Network Pediatric Subcommittee, and chief investigator of the trial at the University of California, San Diego.

Added Jay Hoffnagle, MD, head of the NIDDK Liver Disease Research Branch: "The NASH Clinical Research Network and its two randomized controlled trials offer opportunities to learn more about the cause and natural history of this liver disease."

1. American Liver Foundation. What is NAFLD/NASH? Available at: http://www.liverfoundation.org/db-select/articles/CatNonAlcy/1/1/ascend/Validated. Accessed October 7, 2005.
2. Grant LM, Lisker-Melman N. Nonalcoholic fatty liver disease. Ann Hepatol 2004 Jul-Sep;3(3):93-9.
3. Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE. Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics 2005 May;115(5):e561-5.

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.