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Big Livers Rising

by Laurel Harper

It’s a stealth disease, one that most victims don’t even realize they have until it’s in an advanced stage. Yet up to one out of every four to five Americans suffers from obesity-related liver disease. And it can be a killer.

A healthy normal liver, above, burns fat. However, a liver shown below with the condition known as NASH, or fatty liver disease, stores fat.


In a severe case of NASH, the liver becomes discolored and scarred from the fat accumulation, with dire health consequences.


Normal liver tissue, above, shows little fat, but the liver tissue with NASH below it has large circular white areas of fat.

With nearly two-thirds of all Americans categorized as either obese or overweight, obesity-related disease is the Number One liver problem in America today. Even worse, the number of victims aged 6 to 17 is rising dramatically. In 1970, less than 5 percent of children in the United States were overweight. In 2000, it was 15 percent.

Supersizing and PlayStations are catching up to us, health professionals warn.

Miriam Louthan suspects that the number of overweight children in Kentucky outpaces the national average.

“Twenty percent of the kids who came into our clinic were overweight,” says the pediatric gastrointestinal Fellow in U of L’s Clinical Research Center. “And of those, 9 percent showed evidence of liver disease.”

Louthan and a research team led by Craig McClain—U of L’s department of medicine vice chair for research, director of the university’s new Clinical Research Center and the Bucks for Brains-funded distinguished chair in hepatology—are looking for ways to halt what they believe could become a national epidemic.

“Obesity and obesity-associated problems such as hyperlipidemia, Type II diabetes and hypertension can lead to a fat accumulation in the liver called nonalcoholic steatohepatitis, or NASH. NASH acts just like alcoholic liver disease, only it occurs in people who don’t drink alcohol,” notes McClain, who has studied liver disorders for many years.

“Fatty liver is by far the most common liver problem in the U.S. and is increasingly recognized in children.”

In NASH, fat builds up in the liver and eventually causes scar tissue. When the scarring is extensive, cirrhosis can occur.

As cirrhosis develops, scar tissue surrounds normal liver cells making the tissue bumpy or nodular. This damaged tissue blocks the bile ducts or makes them swell, which then causes bile to back up in the liver and bloodstream. Scar tissue also may block blood flow through the liver, enlarging the veins that bring blood to the liver and leading to high blood pressure in the veins flowing from the intestines to the liver.

Liver failure and death can result. In fact, the four-year death rate for a patient with alcoholic hepatitis and superimposed cirrhosis is more than two-thirds—a dire statistic that surpasses many cancers.

Until fibrosis or cirrhosis occurs, NASH is often symptomless. As an example, McClain cites a recent case in which an overweight Kentucky man in his 40s needed his gall bladder removed. During the operation the surgeon noticed the patient’s liver—he had cirrhosis. “He came here for a transplant but then we found he had liver cancer, too, and he died before anything could be done,” McClain says. “But he’d had no prior signs of liver problems.”

Liver diseases are on the rise, making Craig McClain's work vital. The distinguished chair in hepatology and director of U of L's Clinical Research Center leads a team studying obesity-related liver diseases, hepatitis C and alcohol-related liver disease.


Some childred are developing liver conditions once found only in adults, says Miriam Louthan, a pediatric gastrointestinal Fellow, shown at left with a young patient. Photo courtesy of Geoff Carr.

Occasionally a patient may experience fatigue or discomfort in the upper right quadrant, but generally NASH is detected when bloodwork is being done for another reason and the results show abnormal liver enzymes. That’s why Louthan recommends screening of all obese children.

McClain, who in addition to his research is on the liver transplantation team at Jewish Hospital, warns that the number of people awaiting liver transplants already exceeds the number of organs available. If the problem continues to grow over the next few decades, it could lead to a medical crisis.

“For NASH to advance to full-blown cirrhosis is normally a slow process that probably takes 20 to 30 years, so for someone to get it at my age is less of a problem,” he remarks. “Something else will kill me first.

“But for a 10-year-old, it’s major. There will be a whole population of obese kids growing up who will need liver transplants in their 40s, and we won’t have the medical resources to handle them.”

Some kids, Louthan adds, are experiencing serious problems now. “We were referred a teenager for a liver transplant evaluation a few weeks ago,” she says. “He was overweight and had diabetes. He also had cirrhosis that was likely caused by NASH.”

That’s the bad news. The good news is that NASH is both preventable and treatable. Although there are no widely accepted therapies and the FDA has not approved any drug treatments, McClain and Louthan say that NASH often can be treated with a few simple lifestyle changes.

Getting kids off the couch and onto the playground is a prime way to keep them in good health. Cutting down on their sugar intake is important, too.

“Carbonated beverages are a huge problem,” Louthan notes. “It’s not unusual for some kids to be drinking four or five sodas a day. Sweetened tea and juices are bad, too. Some of the juices have more calories than pop.”

Treating children is easier than adults, both McClain and Louthan agree, as kids are better at making and maintaining lifestyle changes.

“Adults like pills instead,” McClain says.

Studies show that both weight loss and nutritional supplements appear to be beneficial in treating fatty liver in adults. In an article published last year in the journal Hepatology, McClain (who at the time of the study was on staff at the University of Kentucky) and a team of researchers from U of L, UK and the University of Colorado reported on their study of obese patients. All the patients’ liver biochemical tests improved after a three-month weight loss program of diet and exercise, especially those who lost more than 10 percent of their body weight.

But given adults’ proclivity for drugs, the researchers examined several agents and found that among the ones that appeared to help were Vitamin E, betaine and insulin-sensitizing agents.

McClain’s research team at U of L is now focusing on antioxidant therapies. (Some studies show that vitamin E reduces or reverses liver damage, so McClain’s group wants to discover the optimal dosage.) Complementary and alternative medicine (CAM) agents show promise, too.

The team is embarking on a year-long S-adenosylmethionine trial in NASH patients. (S-adenosylmethionine is a dietary supplement sold over the counter under the tradename SAM-e.) McClain’s laboratory also is in the process of developing a new drug therapy for NASH, in conjunction with U of L and the Jewish Hospital Liver Program.

In the meantime, Louthan focuses on working with obese children to change their lifestyles. She also is looking at kids with NASH and comparing them with healthy children to see if she can unearth the mechanisms behind it.

“But unless something changes we expect to see the number of NASH cases continue to increase,” McClain warns.

“This is why people are all worked up about kids not exercising and sitting around playing games and eating supersized stuff at fast food places,” he adds.

“People are aware of obesity and diabetes and hypertension risks. Fatty liver is a big, big problem, too—one that may exceed all these other problems if these kids go on to liver failure 30 years down the line.”

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