NEWS

Racial differences explored in treatment response for hepatitis C

By LESLIE H. LANG
UNC School of Medicine

CHAPEL HILL -- The University of North Carolina at Chapel Hill School of Medicine has been awarded $1.5 million to join seven other medical centers nationwide to determine if blacks respond less well to anti-viral drug therapy for hepatitis C infection than whites.

Hepatitis C is a serious viral infection of the liver transmitted primarily through infected blood and blood products. Approximately 2.7 million Americans and 170 million people worldwide are chronically infected with the hepatitis C virus, often described as "silent" because people may be infected for 10 years to 30 years and not exhibit symptoms, yet still carry the virus. While many patients with hepatitis C will not develop complications from their liver disease, chronic hepatitis C is still a leading cause of cirrhosis and liver cancer and is the major reason for liver transplants in the United States.

The clinical trial is funded by the National Institute of Diabetes & Digestive & Kidney Diseases of the National Institutes of Health. It will study the effectiveness of combination therapy with long-acting pegylated interferon alpha-2a (PEGASYS) and ribavirin, an anti-viral medication. Four hundred patients will be enrolled, equally divided between black and white participants.

The study was prompted in part by statistical analyses of large databases from previous anti-viral studies that suggest racial disparities exist in response to therapy for chronic infection with the hepatitis C virus.

"Major advances have occurred over the last decade in the field of anti-viral therapy for chronic hepatitis C. Unfortunately, response to therapy has not been uniformly favorable across all populations," said Dr. Michael W. Fried, associate professor of medicine and director of clinical hepatology at UNC.

Fried, a principal investigator in the trial, said that sustained response rates in hepatitis C patients have improved to more than 50 percent with pegylated interferon and ribavirin combination therapy, compared to 10 percent to 15 percent for patients treated with interferon alone. Sustained virological response is defined as undetectable blood levels of hepatitis C genetic material (ribonucleic acid) after the treatment-free follow-up period.

But secondary analyses of large databases derived from clinical trials of various anti-viral agents suggest that racial disparities may exist in response to therapy for hepatitis C, particularly when interferon is used as a single agent. In one such analysis, for example, sustained virological response occurred in only 2 percent of black participants in the trial, compared with 12 percent of white participants.

These trials, however, were not designed to study race as a factor in response to therapy. Moreover, few blacks have been included as study subjects, despite the high prevalence of hepatitis C in this population.

Only those with hepatitis C genotype 1 and having quantifiable blood levels (600 IU/ml) of its RNA will participate.

"Those with genotype 1 have the most difficult to treat type of hepatitis C. It is also the most prevalent genotype in the United States," Fried said, adding that it accounts for about 75 percent of hepatitis C infections. It also affects 91 percent of blacks with hepatitis C, compared to 67 percent of whites.

Participants will be treated for 48 weeks with 180 micrograms a week of pegylated interferon alpha-2a plus between 1,000 milligrams and 1,200 milligrams a day of ribavirin. They will be followed for an additional 48 weeks after the therapy ends. Sustained virological response rates (undetectable hepatitis C RNA in serum 24 weeks post-treatment) and durable sustained virological response rates (undetectable hepatitis C RNA in serum 48 weeks post-treatment) between the two treatment groups will be compared to determine differences in treatment response.

Prior to therapy, variables such as gender, history of alcohol use and viral RNA levels will be studied to determine possible factors associated with sustained virological response and how they may differ between the treatment groups.

Potential mechanisms of anti-viral drug resistance will be explored via blood cells sampled from participants at various times in the trial. Among other molecular factors to be studied are measures of interferon signaling pathways and both host and viral genetics.

Other UNC physicians participating with Fried are Drs. Dickens Theodore, Scott Smith, Steven Zacks and Roshan Shrestha.

Along with UNC, participating centers are Beth Israel Deaconess Medical Center in Boston, New York-Presbyterian in New York City, the University of California at San Francisco, the University of Illinois at Chicago College of Medicine, the University of Maryland Medical Center in Baltimore, the University of Miami and the University of Michigan in Ann Arbor.

The UNC Center for Liver Diseases and Transplantation provides highly specialized care for liver diseases for residents of North Carolina and surrounding regions. In addition to its commitment to patient care, the university’s liver program is dedicated to studying novel therapies for viral hepatitis, other chronic liver diseases and transplantation.

- 30 -

Note: Contact Fried at (919) 966-2516 or mfried@med.unc.edu

School of Medicine contact: Les Lang at (919) 843-9687 or llang@med.unc.edu