Team approach and patient motivation critical for NAFLD management

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of liver injury worldwide and the most common cause of chronic liver disease among children in western nations. It includes several disorders associated with excess lipid deposition in hepatocytes, including simple steatosis, nonalcoholic steatohepatitis (NASH) — which is defined by inflammation, cellular ballooning and fibrosis — and cirrhosis.

Patients with simple steatosis rarely show histologic progression. But up to a quarter of children affected with NAFLD have NASH that will progress to cirrhosis, the third leading indication for liver transplantation in the United States.

"If we want to prevent disease progression to cirrhosis, we have to start intervention early in life," says Samar H. Ibrahim, M.B., Ch.B., a pediatric gastroenterologist and hepatologist at Mayo Clinic's campus in Rochester, Minnesota. "Children who are at risk of fatty liver disease will continue to be at risk as adults."

NAFLD was first recognized in children in 1983, and its prevalence has increased with the obesity epidemic, rising from around 4 percent to 10 percent over the last two decades. Both obesity and fatty liver have been linked to two fixtures of the American fast-food diet — saturated fat and high-density fructose, which may have unique metabolic effects that increase the risk of NASH. Although the role of fructose in NAFLD remains a matter of debate, Dr. Ibrahim believes studies in animal models show a clear association between high-fructose consumption and fatty liver.

In addition to obesity, NAFLD is strongly associated with insulin resistance and elevated serum levels of free fatty acids (FFAs) and is considered the hepatic manifestation of the metabolic syndrome, a constellation of metabolic and physiologic abnormalities that can lead to type 2 diabetes and premature cardiovascular disease.

"The metabolic syndrome and insulin resistance overwhelm the body's ability to store lipids, leading to excess saturated free fatty acids in the circulation, which we have shown to be directly hepatoxic," Dr. Ibrahim says. Indeed, FFAs are now thought to be one of the key mediators of liver injury in NASH. Dr. Ibrahim's findings appeared in the Journal of Hepatology.

Diagnosis and management

Most children with NAFLD are asymptomatic, although some may present with abdominal pain. The American Academy of Pediatrics recommends biannual screening of obese and overweight children for elevated serum aminotransferases, starting at age 10, as the best way to identify those with NASH.

Definitive diagnosis requires liver biopsy, which is needed to distinguish simple steatosis from NASH and to exclude other possible causes of liver disease, but due to the risks of the procedure, it is not performed unless a child continues to have elevated liver enzymes and fails to respond to lifestyle changes aimed at weight reduction — the mainstay of treatment.

"Diet and exercise are the way to go in NAFLD," Dr. Ibrahim says. "There are a few medications that may lead to modest improvement, including vitamin E and fish oil, but no established drug therapy. If we see evidence of nonalcoholic steatohepatitis on liver biopsy, we put children on vitamin E, which has been shown to have a beneficial effect on pediatric NASH histological activity. The consensus is not to use vitamin E without a definitive diagnosis, however, because NAFLD is a diagnosis of exclusion, and we don't want to miss other causes of chronic liver disease like autoimmune hepatitis or Wilson disease that might be mimicking it."

Metabolic improvement starts to occur with as little as a 10 percent weight loss, and after one year, patients can lose up to 50 percent of the fat in their liver, effectively reversing the condition. But patients and families are often resistant to lifestyle changes and may not recognize the benefit of weight loss.

"I have seen some families recognize that weight loss is not just about looks but also about preventing serious health problems, and they commit to a diet and exercise regimen. But often, there are barriers to adherence to diet and exercise, and people need a lot of motivation," Dr. Ibrahim says. "We need to follow patients closely every three months, which gives them an opportunity to have their weight checked and gives us an opportunity to emphasize how important it is that they stick to their regimen."

Now, she says, "We're in the process of establishing a pediatric NASH clinic in conjunction with the Pediatric Weight Management Clinic. Pediatric dietitians and social workers play an integral part in managing patients with NAFLD, and this team approach as well as the motivation of patients and their parents are the keys to success."

For more information

Ibrahim SH, et al. Who pulls the trigger: JNK activation in liver lipotoxicity? Journal of Hepatology. 2012;56:17.