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Sikeston native aids in research of disease

Friday, March 3, 2006

ST. LOUIS -- Heavy drinking adults aren't the only ones developing liver disease these days.

As the number of America's obese continues to soar, doctors are finding more serious diseases connected to characteristics of overweight adults.

One disease, in particular, called nonalcoholic steatohepatitis, or NASH, resembles alcoholic liver disease but actually occurs in those who drink little or no alcohol. And once considered to be found only in adults over 40, NASH is becoming a very serious problem for overweight and obese children.

Now NASH has prompted researchers at Saint Louis University to launch a new trial to study NASH in adults and nonalcoholic fatty liver disease -- a spectrum of liver changes that includes NASH -- in children.

Dr. Sarah Barlow said it wasn't until the late 1980s and 1990s that doctors began paying attention to NASH.

"If you don't look for it, you don't find it. The other challenge with NASH is that we don't have a good understanding of who's at risk and how we can stop it," said Barlow, assistant professor of pediatrics at Saint Louis University School of Medicine and a co-investigator of the SLU trials.

For reasons still unknown, some adults and children who are typically overweight or obese will have extra fat deposits in their liver. A small percentage of those with the extra fatty liver will go on to have inflammation and scarring in the liver. Over the years the inflammation and scarring may continue and cause abnormal enzyme levels. As this progresses, it can lead to liver failure.

The study by SLU, which is one of eight clinical centers of the NASH Clinical Research Network conducting the trials, will also test the effectiveness of vitamin E and metformin, a medication used in diabetes, in treating the disease as well as a balanced diet and exercise.

"We don't really know how big of a problem it is," Barlow said. "We do know this change in liver can occur in children who are overweight or obese, and children who are diabetic or pending toward being diabetic are at higher risk."

Barlow, who specializes in pediatric obesity, works with Dr. Brent Tetri, a hepatologist at the Saint Louis University Liver Center and principal investigator of the trials. Tetri said another obstacle to treating NASH is frequent misdiagnosis by primary care doctors.

"Many physicians assume the patient is simply obese or has an elevated liver test," said Tetri, a leading researcher of fatty liver disease and professor of medicine, noting that a failure to correctly diagnose NASH can be dangerous.

Tetri said it's believed the disease is related to behaviors such as eating too much and becoming too sedentary as well as other genetic factors.

"It has all the same risk factors for developing Type II diabetes," Tetri said. But what's challenging for researchers is, for the most part, NASH is symptom-free, Barlow said.

"And that's a worrisome thing," Barlow said.

NASH can remain unnoticed for decades until cirrhosis develops. At that point, patients may experience jaundice, fatigue, mental problems and bleeding, and a liver transplant may be their only option.

Often liver enzymes are abnormal, and this simple blood test is a fairly good screening test although a number of conditions can also make liver enzymes abnormal.

Dr. Elizabeth Matthews Brunt, professor of pathology at SLU, is one of the world's experts in identifying NASH by appearance.

"This disease, unfortunately, as of now can only be diagnosed with pathology," said Brunt, who is a native of Sikeston. "The clinical doctors can exclude other causes of liver disease, but ultimately cannot diagnose NASH without a liver biopsy -- and that's where we come in."

Of the approximate 1,200 biopsies performed at Saint Louis University each year, Brunt estimated a high volume turn out to be NASH.

Though NASH in the early stages seems to have little impact on patients, it can progress to more serious problems and ranks as one of the leading causes of chronic liver disease in the U.S.

"We are seeing people die from this," Tetri said.

Though diabetes and NASH are often linked in patients, NASH can afflict people of normal weight who aren't diabetic; however, Tetri expects about 90 percent of the selected participants will be obese.

The first clinical trial is recruiting 40 local non-diabetic adults over age 18 for two years, and the second trial is recruiting 23 local children between 8 and 17 years old with nonalcoholic fatty liver disease.

The adult participants will undergo liver biopsies at the start and end of the trial. Children enrolled will undergo an initial biopsy, and a second biopsy at the end of the trial will be encouraged but not required.

While there is currently no proven treatment for NASH, results from pilot trials suggest that certain diabetes drugs improve liver enzyme levels and may slow or reverse progression. Other small studies involving patients with NASH showed improvement with antioxidants, such as vitamin E.

Uncovering the progression and treatment of NASH is the main goal of the study, but Barlow said it's important for everyone to keep the lines of communication open with their physicians. And parents, especially, should actively communicate with their pediatricians about maintaining healthy lifestyles for the children, she said.

"The real impact obesity has on children is that they're much more likely than average-weight children to get other diseases as adults," Barlow said. Everyone has to take responsibility for this epidemic, Barlow said.

"It's not just parents who have control over their children's eating habits; we have to hold schools and society accountable, Barlow said. "Ultimately, the health problems cause by this epidemic are going to be very expensive to individuals and society as a whole."

For more information or to enroll in one of the two studies, call (314) 977

-9400.