Hepatitis C is an insidious viral disease that quietly attacks the liver. It often causes chronic liver disease but can show no symptoms for 20 or 30 years after infection. The virus is transmitted through infected blood or body fluids, mainly through the sharing of needles by intravenous drug users.
While the disease has no definite cure, two drugsinterferon and ribavirincan eliminate the virus and limit liver damage in about half the people treated. Interferon can be taken alone but ribavirin is only taken with interferon. The Food and Drug Administration has approved interferon by itself, a regular interferon and ribavirin combination, and a pegylated long-acting form of interferon and ribavirin grouping for use. But a fourth mix, a newer pegylated interferon with ribavirin pair, awaits FDA approval. Patients only need to take pegylated interferon once a week compared with three times a week for regular interferon, and thus is easier to use.
While the drugs have been shown to provide benefit to many patients with hepatitis C, interferon alone and standard interferon with ribavirin appear to be less effective for African Americans than for Caucasians. Pegylated interferon and ribavirin have not been tested on an adequate number of African Americans to assess differences in response rates.
So Dr. Robert S. Brown, associate professor of clinical medicine and clinical pediatrics at P&S, and seven other co-principal investigators at other universities and medical centers set up a clinical trial to investigate the effectiveness of the newer pegylated interferon and ribavirin for African Americans.
The $15 million to $20 million study, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, began recruiting patients in July and will involve a total of 400 patients at eight U.S. centers. Patients will receive 12 months of treatment and 12 months of follow up.
Hepatitis C hits the African American community hard. Of the nearly 4 million Americans or 1.8 percent of the population who have the disease, about 800,000 or 20 percent are African American. There is hope pegylated interferon and ribavirin will be better than regular interferon and ribavirin for African Americans because some studies have shown pegylated interferon in Caucasians can be twice as effective as regular interferon.
Several factors may be playing a role in why African Americans do not seem to fare as well with the medications. The initial clinical trials did not include enough African Americans to make statistically valid conclusions about the findings for them as a group. The pharmaceutical companies testing the drugs did not measure the drugs' effectiveness in diverse populations of patients; rather they tested the drugs in the overall population at selected university centers. The drugs also may not work as well in African Americans because they often carry a strain of the virus more resistant to treatment and they may have less access to proper follow-up care necessary for the drugs to work. Finally, genetic or immunologic differences may be important.
Each center will enroll 50 people: 25 African Americans and 25 Caucasians. The researchers estimate that 200 of each group will allow measurement of clinically significant differences between the groups, if they exist. Having equal numbers of participants at each site also should rule out potential geographic and administrative differences, which could skew results.
To further control for variables, only patients with hepatitis C genotype 1 are being enrolled. Almost all African Americans have the genotype 1 form, which is the most resistant to therapy. About 70 percent of Caucasians with hepatitis C have the genotype 1 version. The drug company-sponsored studies included genotype information in the analysis of medication response but Dr. Brown and his colleagues would like to collect more data on genotype 1, which is responsible for more than 90 percent of hepatitis C infection in African Americans.
The researchers will monitor degree of liver injury, immune system response to the drugs, and genes believed to be important in the response to interferon. They also will assess quality of life to see if factors such as depression, a common medication side effect, play a part in clinical response.
Dr. Brown believes many of the differences attributed to race are overstated.
"The lower response to medication in African Americans seen in earlier studies may be related to differences in care or confusion due to the different disease genotypes," Dr. Brown says. "We want to figure out which factorsif anylead to differential response to these medications, not just between races but between individuals, too."