Fatty Liver Disease: A New Epidemic?
Hardly a day passes without media reports of America’s skyrocketing rates of obesity and type 2 diabetes. Far fewer people, though, are familiar with another disease—closely linked to the first two—that experts say is also becoming an epidemic.
Nonalcoholic fatty liver disease—excess fat in the liver—affects as many as one in five Americans, according to the American Liver Association. But for those with diabetes, says VA physician-researcher Kenneth Cusi, MD, the rate may be as high as four in five. Given that more than a quarter of VA patients are diabetic, fatty liver disease is likely to move up quickly on VA’s agenda of targeted health issues over the next few years.
The disease itself has no symptoms, even when it advances to a more serious form called non-alcoholic steatohepatitis (NASH), in which the liver becomes inflamed and scarred. But people with NASH—probably around 20 or 30 percent of the overall population with fatty liver—can develop advanced scarring, or cirrhosis, and are at higher risk for liver cancer and liver failure. Cirrhosis, marked by fatigue, weight loss, esophageal bleeding and other symptoms, kills some 27,000 Americans per year.
Cusi, an endocrinologist at the San Antonio VA Medical Center and the University of Texas Health Science Center, led a recent study of pioglitazone—a widely prescribed diabetes drug—to treat fatty liver disease. The drug seems to be a “perfect fit,” he says, since it helps insulin resistance and improves blood-sugar control—both major factors in the development of NASH. As of now, the drug, sold as Actos, is approved by the Food and Drug Administration only for diabetes; physicians treating fatty liver disease usually recommend only weight loss.
Diabetes-liver link long overlooked
While it might seem obvious that a diabetes drug could help fatty liver disease, given the shared metabolic underpinnings of the two conditions, the connection had largely been ignored until recently. Cusi explains that while most diabetes patients may in fact have fatty liver, they typically don’t have elevated liver enzymes, which would prompt primary care doctors or endocrinologists to order a biopsy or other tests to check for liver trouble.
It was only through research on other diabetes-related issues that Cusi’s group discovered the liver connection. "We were looking at diabetics for other reasons," he said, "and we were finding that fatty liver was far more common than we thought."
Poor diet leads quickly to fatty liver, diabetes in mice
The trial his team conducted, funded in part by drug manufacturer Takeda, included 55 men and women. All were overweight or obese, and all had NASH—as confirmed by liver biopsy—plus either diabetes or glucose intolerance, also known as pre-diabetes. Participants cut their calorie intake and were randomized to either pioglitazone or a placebo.
In addition to other measurements, the researchers used magnetic resonance spectroscopy to measure fat in the liver before and after treatment. "It’s the gold standard for examining the amount of fat in the liver,"notes Cusi. "Only a few centers in the U.S. have this available."
Diabetes drug cuts fat in liver
After six months of treatment, the medication group saw a 54-percent reduction in their liver fat, while the placebo group had no reduction at all. The drug group also saw more favorable results in most other measures, such as insulin sensitivity, glucose metabolism, triglyceride levels and liver inflammation. On the down side, those volunteers taking pioglitazone gained two or three pounds on average—a known side effect of the drug—while the placebo group stayed about the same weight. As long as patients are careful with diet, says Cusi, added weight should be more than offset by the benefits of treatment.
The results appeared in the Nov. 30, 2006, New England Journal of Medicine. Cusi calls the study an "exciting first step," but points out that the results will need to be replicated in larger trials of longer duration.
Screening study to include up to 250 veterans
Meanwhile, another trial has begun at the Cleveland Clinic and Case Western Reserve University to test the benefits of pioglitazone for fatty liver. And researchers around the world are exploring a variety of other approaches as well, ranging from conventional to alternative: other diabetes drugs, weightloss surgery, vitamins, essential fatty acids, cinnamon and other herbs. But results so far are preliminary and quite mixed.
For his part, Cusi is securing final approvals for a screening study to involve up to 250 veterans with diabetes. The goal will be to get a better handle on the prevalence of fatty liver disease. The VA researcher points out that his site, San Antonio, with its large Hispanic population, is a "hotbed" for both diabetes and fatty liver disease, and may be an ideal setting in which to learn more about both conditions.