Doctors see increase in patients with serious liver disease

Illness can progress to cirrhosis, and transplants may be the best option



Richard Cavasina was lying in bed one night in October 2009 when he felt some fluid come up his esophagus into his mouth. Thinking it was saliva, he went into the bathroom to spit it out. Instead he spit out blood -- a lot of it.

It turned out he had enlarged esophageal veins called varices and one of them had burst -- a complication of nonalcoholic steatohepatitis that had progressed to cirrhosis of the liver. Mr. Cavasina, now 61, of Peters, was hospitalized three days before doctors were able to get his blood to clot with an intravenous medication.

"That's when it really dawned on me: This is really serious," he said.

It would get much more serious. Mr. Cavasina, a professor of psychology at California University of Pennsylvania who was diagnosed with cirrhosis about three years ago, has been on the list for a liver transplant for more than a year, said liver transplant specialist Ngoc Thai of Allegheny General Hospital, director of the AGH Center for Abdominal Transplantation. Mr. Cavasina said he was told in July he should get one in six months to a year.

Nonalcoholic steatohepatitis is the most serious form of nonalcoholic fatty liver disease, or hepatic steatosis, which is an accumulation of fat in the livers of people who drink little or no alcohol.

NAFLD (pronounced NAF-EL-DEE), as liver specialists call nonalcoholic fatty liver disease, affects tens of millions of Americans and is usually harmless. "Fatty liver disease nowadays is practically an epidemic in this country," said hepatologist Jose Oliva, medical director of the AGH Liver Transplant Program.

Nonalcoholic steatohepatitis, or NASH, is another story. Patients can develop inflammation and scar tissue in their livers, which can progress to chronic liver disease. That in turn can progress to cirrhosis and "its complications, primary liver cancer and, in some cases, may require transplantation of the liver," said Kapil Chopra, director of UPMC's Center for Liver Disease.

That's what happened to Mr. Cavasina.

The esophageal varices he developed result because blood no longer flows easily through the scarred liver, and the blood backs up into smaller vessels, causing them to swell and, sometimes, burst.

Mr. Cavasina's varices led to several procedures in which Dr. Oliva put a scope down his esophagus and used rubber bands to shut off the bleeding. "I think it was 21/2 months before he had them under control," Mr. Cavasina said.

Also as a result of the increased pressure, he developed ascites, an accumulation of fluid in the abdomen.

"He required that the fluid be removed with a needle several times," Dr. Oliva said. Then, over the Fourth of July holiday, doctors put a stent in his liver to drain the excess fluid and control the pressure. Mr. Cavasina said he lost 50 pounds with the surgery.

It was during that hospitalization that he told Dr. Thai he had "no fuel in my tank" and asked how soon the transplant might occur.

"You're saying I have to have a transplant, and what happens if it doesn't work?" he asked. "... That's when you start to go through the real fear factor: Even though I'm in the hands of what are probably two of the best surgeons in the country, I can still die from this."

How many of the estimated 6,000 people who annually undergo liver transplants nationally have done so because of cirrhosis that progressed from nonalcoholic steatohepatitis wasn't available, Dr. Thai said. But, he said, "the number [has been] increasing over the past 10 years."

At AGH, though, where more than 50 livers have been transplanted since the program started in 2007, "the estimate is about 10 to 15 percent are from NASH," he said.

At UPMC, approximately 20 percent of the 110 to 125 livers transplanted each year results from NASH that has progressed to cirrhosis, Dr. Chopra said, and this figure too appears to be increasing.

Estimates of how many millions of people have nonalcoholic fatty liver disease and the more insidious nonalcoholic steatohepatitis vary.

"The prevalence of NAFLD in the general population in Western countries ranges from 20 to 30 percent, and between 5 and 10 percent of people with NAFLD will have NASH," Dr. Chopra said.

In comparison, the prevalence of hepatitis C in the United States is estimated to be between 2 and 3 percent, he added.

Although experts believe more than one problem is involved, insulin resistance and its manifestations are often associated with NAFLD and, as a result, NASH. In insulin resistance, your body resists the effects of the hormone that helps to regulate the amount of sugar in your body, and the pancreas tries to compensate by making more insulin.

"We think the basic problem is insulin resistance [because] insulin levels are very high," Dr. Oliva said. "That causes the fat to accumulate in your liver." Once there, the fat starts interacting with liver cells and causing damage.

Manifestations of insulin resistance, Dr. Chopra said, include obesity, an accumulation of belly fat, type 2 diabetes, high arterial blood pressure and a high level of triglycerides, the major form of fat stored in the body.

"There are certain things that can cause fatty liver. The most common are obesity and diabetes," Dr. Oliva said. Other causes include high cholesterol, certain diseases and some medications.

"So readers can grasp the magnitude of this, 80 to 90 percent of obese people will have fatty liver and about a third of them will have steatohepatitis. So you can see it's a widespread, significant problem because at least half of the population is overweight and obese," he added.

"... What number of those will have steatohepatitis would be a minority, but still, a minority of so many patients is still a large number."

Sometimes thin people get steatohepatitis, too.

"That's strange there are skinny people who have NASH," Dr. Thai said, adding that he suspects there may be genetic or autoimmune components involved as well.

Dr. Chopra said the prevalence of nonalcoholic fatty liver disease also increases with age, is highest in males ages 40 to 65, and has an ethnic distribution higher in Hispanics, lower in African Americans. "Family members of subjects with NAFLD are at increased risk," he added.

Nonalcoholic fatty liver disease is hard to diagnose because there are no specific symptoms.

"By the time symptoms are recognized it is usually an advanced state of the liver disease," Dr. Chopra said.

There are three ways to catch it earlier: the primary care physician recognizes risk factors such as the patient being overweight or having diabetes; blood tests and imaging such as ultrasound, CT scans and MRI; or a biopsy of the liver, he said.

If diagnosed, treatment still is "very difficult," Dr. Oliva said. It includes exercise, losing weight, tight control of blood sugars by diabetics, and tight control of cholesterol if levels are high. Sometimes doctors also use Vitamins E or C. Dr. Chopra said studies have indicated E can be beneficial, "however, long-term outcomes remain to be seen."

What local experts do expect to see is an increase in nonalcoholic steatohepatitis.

"Clearly NASH will be a bigger public health issue in the years to come," Dr. Chopra said.


Pohla Smith: psmith@post-gazette.com or 412-263-1228. First Published August 22, 2011 4:00 AM


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