childhood_obesityIt’s often said, these days, that we’re a nation of fatties. And, not coincidentally, we’re also a nation of fatty livers.

Increasingly, millions of those livers belong to children – though most of them don’t know it, and neither do their parents and doctors.

Usually, no symptoms show up until damage has been done, damage that may ultimately lead to cirrhosis of the liver, liver cancer and end-stage liver disease.

Until the 1990s, no one knew that fatty livers were a problem in children, and now, doctors say, the situation has become serious. “If you were to go into any large California high school with a couple thousand students and screen, you’d expect 200 children with fatty livers,” says Dr. Jeffrey Schwimmer, director of the Fatty Liver Clinic at Rady Children’s Hospital in San Diego and associate professor of pediatrics at UC San Diego.
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Schwimmer was lead author of a study published in the journal Pediatrics in October 2006 that found evidence that nearly 10% of children between 2 and 19 years old in San Diego County have fatty livers. If that percentage holds throughout the U.S., 6.5 million children are affected.

The data show that fatty livers in children are highly correlated with weight. About 80% of kids with the condition are obese or overweight. Nearly 40% of obese children have fatty livers.

“It’s the most common serious complication of childhood obesity,” Schwimmer says. And doctors fear it may cause serious problems for these children as adults. In a study published in the October 2006 issue of the journal Hepatology, researchers in Sweden followed up on adult patients an average of 14 years after they were diagnosed with fatty livers and found that most of them had diabetes or impaired glucose tolerance. Many had end-stage liver disease.

Experts say it is likely that children with fatty livers have a head start on these problems and may be at risk for developing them while still young.

To date, biopsies are the only effective diagnostic test for fatty livers. Diet and exercise are the only effective treatments. And it’s a mystery why the condition can be harmless for many, yet dangerous for others.

Under-the-radar disease

People with fatty livers are said to have nonalcoholic fatty liver disease. By definition, this disease occurs when 5% or more of the liver is fat. Often no damage is done, but in about 20% to 25% of cases, excess fat in the liver results in cell destruction and inflammation. At that point it becomes a condition known as nonalcoholic steatohepatitis, a form of hepatitis caused not by a virus but by too much fat.

People can have nonalcoholic fatty liver disease, even nonalcoholic steatohepatitis, without symptoms. “And they won’t have until they show up in the emergency room with a life-threatening problem,” Schwimmer says.

Nonalcoholic steatohepatitis can sometimes lead to cirrhosis of the liver, a scarring of tissue that impairs function. These days, doctors have even seen cases of 8-year-olds with cirrhosis of the liver.

Besides weight, the disease is related to age, ethnicity and gender. It’s more prevalent in adolescents than in younger children, most prevalent in Latinos (12%) and least in blacks (less than 2%) and more prevalent in boys than girls.

Schwimmer’s study, the only prevalence study to date, was done by reviewing autopsy records over 10 years, which is perhaps the only way to obtain that kind of data right now. Some screening for fatty liver disease is possible with blood tests that look for elevated levels of liver enzymes, as well as ultrasound or magnetic resonance imaging. But these methods are very imprecise. Accurate diagnosis requires a biopsy.

“We need a good diagnostic test that’s simple, cheap and reliable,” says Dr. Ariel Feldstein, assistant professor of molecular medicine at Ohio’s Cleveland Clinic. Feldstein heads a team that may have developed such a diagnostic, at least for nonalcoholic steatohepatitis: a simple blood test that proved accurate in a small study published in the journal Hepatology in July 2006.

The test is based on the discovery that patients with nonalcoholic steatohepatitis have a fragment of a protein called cytokeratin-18 in their blood, as a byproduct of the type of liver cell death that nonalcoholic steatohepatitis causes. A larger study of this test is ongoing.

Research also is underway at UC San Diego to develop accurate, noninvasive diagnostic methods for nonalcoholic fatty liver disease, including the use of spectroscopy.

So far, diet and exercise are the only effective treatments for correcting fatty livers so that more damage, at least, isn’t done. “Unfortunately, people aren’t good at doing those things,” says Dr. Jean Molleston, clinical professor of pediatrics at the Indiana University School of Medicine/Riley Hospital for Children.

But several studies of possible medications for children are planned or in progress, including large clinical trials to test vitamin E and metformin, a drug used to treat diabetes.

Search for treatment

The two treatments are directed at different aspects of fatty liver disease. Excessive fat in liver cells is known to cause oxidative stress that, in turn, can lead to scarring. Vitamin E’s antioxidant properties may decrease that stress.

Almost all children with nonalcoholic fatty liver disease are insulin resistant – their body cells don’t respond to normal amounts of insulin the way they should. Metformin makes cells more responsive.

In pilot studies, both treatments improved patients’ blood chemistry, and metformin also lowered fat content in the liver.

There are currently no data to show what the long-term prognosis is for children with fatty livers. But there’s concern that, with a lifetime ahead of them, they’ll have plenty of time for bad consequences to develop.

Researchers are looking for ways to predict who will luck out and avoid those consequences, and who won’t. They’re finding that there is some correlation between bad outcomes and just how fatty the liver is.

“If someone has 40% fat, they are more likely to have [nonalcoholic steatohepatitis] than someone with 5% fat” in their livers, Schwimmer says. “But there are some people with [nonalcoholic steatohepatitis] and even cirrhosis with relatively small amounts of fat. I saw a child recently with cirrhosis and only 8% fat.”

Schwimmer believes that nonalcoholic fatty liver disease has a large genetic component, and he’s studying it in families. He’s also comparing groups of children with different likelihoods of having fatty liver disease – whites, blacks and Latinos, both male and female. Using blood tests and total-body MRIs to see how the children store fat, he hopes to find similarities within and across groups that might explain the different rates.

It’s known, for example, that girls store fat in their bodies differently from how boys do. That might be related to why boys are more likely to get the disease.
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Meanwhile, many experts say screening for nonalcoholic fatty liver disease should be standard practice – at least with obese patients – even though current methods aren’t perfect.

“We ought to be doing it,” Molleston says. “That’s my personal opinion – I think I’m right about it, though.”

By Karen Ravn

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