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Inside Tract - Introducing our next epidemic, fatty liver disease

Inside Tract Summer 2011

Introducing our next epidemic, fatty liver disease

Date: June 1, 2011

Ayman Koteish explains why things must change.

“There’s a smoldering, scarring asymptomatic progression in this type of fatty liver disease,” Ayman Koteish explains.
“There’s a smoldering, scarring asymptomatic progression in this type of fatty liver disease,” Ayman Koteish explains.

It takes a special skill set to deal with nonalcoholic fatty liver disease (NAFLD).

Because many factors seem to prompt it, the onset is subtle and its progress silent, as a rule. The genetics, so far, is uncertain. Therapy proves unsatisfactory once cirrhosis is under way.

That’s why hepatologist Ayman Koteish is most comfortable approaching the illness on multiple fronts. Koteish specializes in liver disease and its outcomes; he’s a co-researcher in population studies, a contributor to association studies looking for susceptibility genes and a basic scientist researching the liver fibrosis that can turn NAFLD end-stage.

Here he shares his insights.

You’ve mentioned the shocking statistic that possibly a third of Americans have a fatty liver. How can that be?

The figure comes from the well-designed Dallas Heart Study that’s diverse enough to apply its conclusions nationwide. The research used sensitive MR spectroscopy to detect liver fat. Other work*, a CDC-based study of 15,000 Americans, estimates undetected fatty liver disease at 5 percent, based, indirectly, on elevated liver enzymes. Either way, these trends make it clear that fatty liver disease is becoming this nation’s next epidemic.

We used to hear that NAFDL is a “two hit” disease, that first there’s the fatty liver, then something causes inflammation and triggers its advance.

Yes, but that’s changed recently. Now we believe that a conglomeration of events takes place simultaneously to cause hepatic inflammation and cell death. Luckily, most individuals—some 70 percent— stay at the fatty liver stage.

Why? Why do some go about life with fatty liver and other people have repeated scarring, then cirrhosis and death?

That’s the jackpot question. There’s not necessarily one cause but multiple interacting factors that cause it to progress, and they largely seem to be associated with the metabolic syndrome.


We don’t know exactly. But we do know that insulin resistance—part of the metabolic syndrome—encourages an uncontrolled wash of free fatty acids into the liver, and fatty liver ensues. Because free fatty acids can be liver toxic, things go downhill from there. Obesity plays its part since the deep belly fat that surrounds intestines is an ample source of those fatty acids.

So how do you help?

By identifying people while they’re still asymptomatic. Patients are often referred to our liver clinic with unexplained elevated liver enzymes. Many of them also have diabetes and high blood pressure—both contributing factors to NAFLD—though no signs of entrenched liver disease. We could tell them, Your liver is basically OK for now. Go home.

But we’re aware of the disease’s course and its statistics. Seventy percent of diabetics have fatty liver. Should they also develop inflammation, half of them will die early from liver-related complications, barring a transplant. As many as 7 percent will develop hepatocellular carcinoma within 10 years of diagnosis.

 So we aggressively treat their diabetes as well as the insulin resistance that presages it. We’re proactive with their hypertension, their hyperlipidemia. We prescribe a specific vitamin E isomer to reduce inflammation.

So you may need to follow patients for decades?

Yes. There must be long-term integration of care—you orchestrate it. That’s sometimes difficult to justify to insurers in the setting of this economy and present health care status. And it’s something we need to explain to patients, who, without symptoms other than fatigue, would be bewildered.

And in the lab, you model NAFLD?

Yes. We also model the scarring aspect. By creating a variety of mouse models that go to end-stage liver disease—some carry suspect human genes, some mimic alcoholism, some eat a fast food diet—we are more likely to find a common molecular path to study and, ultimately, single out for therapy.

  * the NAHNES-III study