University Times

Pitt's Graduate School of Public Health (GSPH) is coordinating a national, multi-site study that will — for the first time — examine differences in how blacks and whites respond to the latest, best treatment for hepatitis C, an infectious disease affecting some 4 million Americans.

The National Institute of Diabetes and Digestive and Kidney Diseases has awarded Pitt $7.7 million to coordinate the trial.

"We are experiencing an epidemic of hepatitis C-induced liver disease in the United States, and the treatments used to treat hepatitis C have not worked well, particularly among African-Americans," said principal investigator Steven Belle, associate professor of epidemiology and biostatistics, referring to smaller studies showing that blacks respond poorly to treatment for hepatitis C.

"Through this study, we will determine whether African-Americans indeed have a poorer response rate to treatment, and if so, why. The results will lead to more effective and appropriate treatments for different groups of people."

Regardless of whether race plays a part, the trial will seek to discover why people respond differently to hepatitis C treatment.

"We're looking at different potential reasons, including the virus itself," Belle said. "Is it that some people are infected with different forms of the virus? It could be that some strains are more resistant to treatment. Or, it may be related to differences in how individuals respond to infections. We will look at patients' immune responses and responses to therapy, as well as their genetic backgrounds."

Hepatitis, an inflammation of the liver, takes several forms. Types B and C are the most serious, often leading to permanent liver damage. Hepatitis C infection results most often from recreational IV drug use, hemodialysis, tattoos, body piercing or blood transfusions that took place before screening for the virus began in 1990. Hepatitis C infection is disproportionately high among African-Americans.

Symptoms can take up to 20 years to develop. Many people carry hepatitis C unknowingly and can transmit it to others. The virus can lead to cirrhosis, liver cancer or liver failure, and is the main reason for liver transplants in the United States. The rise in incidence of liver disease in recent years is a result of the equally dramatic rise in hepatitis C infection in the 1960s, '70s and '80s, according to Belle.

"The actual incidence of new hepatitis C infections is probably on the way down," he said. "But blood transfusions and recreational drug use were more common in the 1960s than in previous years. Those are probably the two main reasons we're seeing this current epidemic."

Several treatments have been used for hepatitis C over the past decade, including interferon, interferon combined with anti-viral therapies, and a newer interferon administered as a weekly shot.

"None of the medications used to date for hepatitis C have worked well, and they often cause serious flu-like side effects," Belle said.

In the GSPH-coordinated study, investigators will recruit 400 hepatitis C patients (200 blacks and 200 whites) at each of eight clinical sites around the United States. Each participant will receive pegylated interferon, a newer type of interferon with larger molecules that remain in the body longer, combined with the anti-viral medication ribavirin, which enhances the effects of interferon. This combination was approved recently by the U.S. Food and Drug Administration for treatment of hepatitis C.

After patients have been treated for one year, researchers will determine whether there are outcome differences between blacks and whites, and the clinical, biochemical, virological, cellular, immunological and genetic factors that could be responsible for any differences.

For instance, studies have shown that interferon therapy is impaired by iron overload, which is thought to affect some 30 percent of the black population in the United States, and by the presence of fat in the liver, which is influenced by age, gender, body mass index, body composition, alcohol use, diabetes, insulin resistance syndromes and cholesterol level.

Also, investigators will look at viral kinetics, or the rising and falling of viral load. "Currently, we notice a quick drop in viral load after therapy is initiated, and then the drop slows down," Belle said. "Different people have different patterns of viral kinetics, and we want to know if these patterns can tell us who will ultimately respond to a treatment."

Pitt will coordinate the project but will not be a trial site. Sites include the University of Maryland, the University of North Carolina, the University of Illinois, the University of California-San Francisco, the University of Michigan, Beth Israel Deaconess Medical Center, Columbia University and the University of Miami.

— Bruce Steele