African American patients with hepatitis C (HCV) infections experience a lower response rate to the peginterferon alfa-2a and ribavirin combination treatment than Caucasian Americans*, according to a study published in the August issue of Gastroenterology, the journal for the members of the American Gastroenterological Association (AGA).
Racial differences in viral responses were seen as early as the fourth week of treatment. A pegylated interferon combined with ribavirin is standard therapy for HCV.
Researchers from the Study of Viral Resistance to Antiviral Therapy for Chronic Hepatitis C (Virahep-C), which is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), conducted the study to determine the potential mechanisms of antiviral resistance among patients who fail to respond to current optimal therapy regimens. While African Americans have a higher prevalence of HCV infection, they have been underrepresented in most therapeutic clinical trials, making it difficult to estimate response rates in these patients.
According to Charles Howell, MD, associate professor of medicine, University of Maryland School of Medicine and chairperson of the Virahep-C Study Group Steering Committee, "The basis for the racial difference in virologic response rates is being addressed by ongoing supplementary studies in genetics, immunology, interferon signaling and pharmacology, and virology. However, our study results indicate that the reduced response rate among African American patients is not caused by the usual predictors such as patient age, gender, pretreatment serum HCV concentrations, amount of fibrosis in the liver biopsy nor amount of medication taken."
Study results showed that sustained virologic response (SVR), the primary endpoint, was significantly lower in African Americans compared with Caucasians (28 percent vs. 52 percent; P<.0001). Patients with SVR had not shown evidence of HCV RNA in their blood 24 weeks after the end of treatment. At treatment week 24, 46 percent of African Americans compared with 74 percent of Caucasian patients were HCV RNA negative and were eligible to continue on therapy to 48 weeks. While breakthroughs in virologic response during treatment were more common among African Americans than Caucasian patients (13 percent vs. 6 percent), the relapse rates after treatment were comparable (32 percent vs. 25 percent).
Data indicated that the proportion of the total maximum dose taken of both peginterferon and ribavirin during the first 24 weeks of treatment was significantly less in African Americans versus Caucasian patients; 54 percent of African American patients compared with 73 percent of Caucasian patients took at least 80 percent of the maximum doses of both peginterferon and ribavirin (P<.0001). However, this did not account for the racial difference in SVR rates.
African American and Caucasian patients experienced similar serious adverse events, dose reductions and drug discontinuations. Three deaths were included in the serious adverse events for African American patients - two deaths were considered unrelated after therapy had stopped, and one death occurred during therapy, possibly related to the peginterferon treatment.
Study Design Patients were treated for up to 48 weeks with peginterferon alfa-2a (Pegasys.) 180 5g/wk and ribavirin (Copegus.) 1000 or 2000 mg/day based on body weight of 75 kg or less. Patients were monitored at one to two week intervals for the first eight weeks, then every four weeks through the end of the study. Virologic response was assessed at week 24, and treatment was stopped in patients who had a positive test for serum HCV RNA. Responders continued treatment for another 24 weeks and were assessed for sustained virologic response at 24 weeks after treatment completion.
The study enrolled 401 patients (196 African Americans and 205 Caucasian Americans) who were treated at eight U.S. clinical centers between July 2002 and December 2003. Both groups were similar in terms of sex, age, estimated duration of infection, suspected source of infection and alcohol use. African American patients had a higher body weight and were more likely to have a history of diabetes and hypertension. African Americans were also more likely to have genotype 1b and less likely to have genotype 1a.
According to a second study published in the August issue of Gastroenterology, "non-Hispanic black race [is] the important predictor of genotype 1, and among persons infected with subtypes 1a and 1b, older age and non-Hispanic black race were the important predictors of genotype 1b...genotype1 and non-Hispanic black race, have been associated with a reduced response to antiviral therapies."**
Hepatitis C Surveys indicate that 1.3 percent of the U.S. population, approximately 3.2 million Americans, have chronic HCV. Chronic HCV is the leading cause of chronic liver disease and the most common indication for liver transplants in the U.S. HCV-related cirrhosis (disruption of normal liver function caused by various chronic progressive conditions) accounts for almost 50 percent of newly diagnosed liver cancers and approximately 10,000 deaths per year.
*Conjeevaram H, Fried M, Jeffers L, Terrault N, Wiley-Lucas T, Afdhal N, Brown R, Belle S, Hoffnagle J, Kleiner D, Howell C. Peginterferon and Ribavirin Treatment in African American Patients and Caucasian American Patients with Hepatitis C Genotype 1. Gastroenterology 2006; 131:470-477.
**Nainan O, Alter M, Kruszon-Moran D, Gao F-X, Xia G, McQuillan G, Margolis H. Hepatitis C Virus Genotypes and Viral Concentrations in Participants of a General Population Survey in the United States. Gastroenterology 2006;131:478-484.