Â鶹´«Ã½

News — It's another result of an aging baby boom population: an upsurge in cases of liver cancer and other forms of liver disease caused by years of chronic infection with a virus many people don't even realize they have.

Fortunately, scientists at an upcoming international conference will report that improved ways of stopping hepatitis C are on the horizon.

Approximately 3.2 million people in the United States are believed to be chronically infected with hepatitis C, or HCV, with the highest incidence among people in their 40s to 60s. Worldwide, approximately 170 million people are believed to be infected.

For years, hepatitis C has been called the "silent epidemic," because a chronic infection can persist for decades before causing symptoms, such as cirrhosis of the liver. Cirrhosis itself can be fatal, with scarring that impairs liver function and blood circulation, and can lead to liver failure.

Hepatitis C infection is already the leading cause of liver transplants in this country, but now the United States is also experiencing an increase in the rate of HCV-related liver cancer. In fact, "liver cancer is now America's most rapidly increasing form of cancer, and as the epidemic of HCV-infected individuals ages, we're only going to see rates of liver disease get higher and higher," said Robert Lanford, Ph.D., a researcher at Southwest Foundation for Biomedical Research and one of the organizers of the upcoming conference. "So it is especially exciting that the international research community has some good news to report on the development of powerful new antiviral medications to treat HCV infection."

800 scientists to convene

The 15th International Symposium on Hepatitis C & Related Viruses will bring together 800 international scientists from Oct. 5-9 at the Marriott Rivercenter in San Antonio. The meeting will be co-chaired by two Texas scientists, Dr. Lanford of San Antonio's Southwest Foundation for Biomedical Research (SFBR), and Stanley Lemon, M.D., the John Sealy distinguished university chair and director of the Institute for Human Infections and Immunity at the University of Texas Medical Branch at Galveston. The two scientists and their institutions also collaborate as part of the Southeastern Hepatitis C Cooperative Research Center, which also includes researchers from Johns-Hopkins University in Baltimore, Md., and the University of Washington in Seattle, Wash.

At the San Antonio symposium, 450 presentations from scientists from around the world will provide an overview of the history of HCV and current statistics on disease prevalence and trends, as well as the latest in biomedical research aimed at treating and preventing HCV infections.

This year's conference holds special importance for the HCV research community because it marks the 30th anniversary of the development of an animal model for studying the disease, the chimpanzee. At the time, HCV had not been specifically identified, and was called "non-A, non-B hepatitis," a reference to the virus not being hepatitis A virus or hepatitis B virus, the two hepatitis viruses that were known at the time. Many of the major breakthroughs in treating the disease and screening the blood supply for HCV contamination have been advanced by research with chimpanzees.

Developing better drugs

HCV researchers worldwide are trying to develop an antiviral treatment to replace the only U.S. Food and Drug Administration-approved therapy for hepatitis C, a 48-week regimen of pegylated interferon-alpha and ribavirin, which causes severe flu-like symptoms and a number of other side effects. And the cure rate is less than 50 percent for those enduring the side effects of these two drugs.

Because HCV mutates rapidly, combinations of drugs are needed to compensate for the rapid resistance the virus can easily develop to any single drug. Researchers would like to develop a cocktail of three drugs to cure HCV with greater efficacy and without the toxicity of the current therapy that some patients cannot tolerate.

"We believe that if we get three really good antivirals that target the virus at different required functions, mathematically, the chance of having three genetic changes in the same virus so that it can escape all three antivirals simultaneously is remote," Lanford explained. He said that researchers attending the conference in San Antonio will make over 80 presentations related to improved antiviral treatments, as well as updates on the progress to develop a preventive vaccine, which so far has proven difficult to accomplish.

About 30 new antivirals are in various stages of clinical trials, said Lanford, whose laboratory tests many of the new HCV drugs in chimpanzees at SFBR's Southwest National Primate Research Center before the drugs receive approval for trials with people.

The chimpanzee remains the only animal model for HCV. Because of the animal's physiological similarity to humans, it provides essential data on how well the body "takes up" a drug therapy, how well the drug reaches the circulation and the liver, and how long before the drug disappears.

"That tells you how to design your clinical trial, whether people are taking the drug once a day, twice a day, or three times a day," Lanford said. "It's what we call 'PK,' pharmacokinetics."

Tests with chimpanzees also reveals how potent a drug is, or how quickly it reduces the level of the virus in the blood.

Because of these and other factors, chimpanzees at SFBR were instrumental in the development and testing of a vaccine for hepatitis B, the leading cause of liver cancer in much of the world. Today, the hepatitis B vaccine is routinely administered to children in the United States and many other countries. Lanford says that current work with this research model is now yielding exciting breakthroughs in the treatment of hepatitis C.

Some of the most promising new HCV drugs undergoing testing at SFBR have shown a 10,000-fold suppression of the virus in just two days, reducing viral load from 1 million copies per milliliter of blood to only 100 per milliliter, Lanford said.

"Five years ago, we were lucky to see a 10-fold suppression in virus from the drugs that were being developed," he said. "In the last few years, we've been seeing this class of highly potent drugs that attack different targets on the virus, such that they can be used in combination in a cocktail."

Sources of infection

People acquire HCV when blood from an infected individual gets into the bloodstream. Although many with the virus acquired it via blood transfusions or exposure to blood products, the United States saw a spike in HCV infection when intravenous use of illegal drugs increased among young people in the mid-1960s. The infection rate peaked in the mid-1970s.

A major source of infection prior to the ability to screen the blood supply for HCV was related to medical procedures. Those included medical advances of the 1960s, such as coronary bypass surgery, requiring an increased need for blood transfusions, and an increased likelihood that those having surgery would receive contaminated blood, Lanford said. In addition, many hemophiliacs requiring regular blood transfusions, as well as kidney dialysis patients, acquired the disease from their medical treatments.

HCV was not identified as a separate virus until 1988, and screening to detect the virus in donated blood was not developed until 1989. The initial cloning or identification of the virus was accomplished by scientist at Chiron laboratories using blood from an infected chimpanzee. Dr. Michael Houghton, a keynote speaker at the symposium, was the leader of the group that isolated the virus at Chiron.

Silent no more

"Unfortunately, the silent part of this epidemic really disappeared a long time ago," Lanford said. "The infection is 'silent,' or asymptomatic, for the first few decades, but as you progress in age, and as the duration of the time you have been infected increases, the likelihood that you are going to progress to cirrhosis increases and increases. So eventually we expect that over 20 percent of infected individuals will develop cirrhosis. That's a very large group of people."

According to the Centers for Disease Control and Prevention, about 3.2 million people in the United States, or nearly 2 percent of the population, have chronic HCV infection. About 4 percent of those 35-60 years old carry the virus.

In the United States, HCV is the leading cause of liver cancer, which is the most rapidly increasing form of cancer. Other forms of cancer, such as lung and breast, are more prevalent than liver cancer, but their incidence is declining in frequency as we change lifestyle and develop better treatments.

Because some highly improved treatments for HCV are expected to be available in the future, many patients are postponing treatment if they are not yet showing advanced-stage symptoms of the disease.

"I am an optimist about the newer therapies. The anticipation is that in five or 10 years, we will have three good drugs, or a cocktail, without the harsh toxicity of interferon and ribavirin," Lanford said, "and we will be in a good position to cure this epidemic."

Southwest Foundation for Biomedical Research is one of the leading independent biomedical research institutions in the United States, dedicated to advancing human health through innovative biomedical research. It is recognized within scientific and academic communities worldwide for the quality of its basic research into the nature, causes, preventions, and treatments for disease. SFBR's staff of more than 85 doctoral-level scientists conducts nearly 200 major research projects, with marked success in the areas of genetics, neonatal development, metabolic disorders and infectious diseases.