We'll be providing some additional context and perspectives on the controversy surrounding Schering-Plough's initial exclusion of African Americans from its phase II study of SCH 503034, a new hepatitis C protease inhibitor (see previous post). Today, here's some background on African Americans and hepatitis C, focusing on epidemiology and response to treatment.
What do we know about African Americans and hepatitis C?
Epidemiology: African Americans have a higher rate of hepatitis C than other racial/ethnic groups – 3.0% of African Americans have been infected with hepatitis C, twice as high as the rate among whites. Hepatitis C prevalence is highest among black males ages 45-49: an alarming 17.9% have been infected, according to statistics from the Centers for Disease Control and Prevention (CDC), a federal agency. Though African Americans make up roughly 12% of the U.S. population, they account for an estimated 22% of all people with chronic hepatitis C in the country.
Treatment: Hepatitis C treatment is much less effective in African Americans compared to other racial/ethnic groups. Part of the decreased success of treatment is linked to genotype – among people with chronic hepatitis C, roughly 90% of African Americans have genotype 1, the strain of hepatitis C least responsive to interferon-based treatment, compared to about 70% of whites. However, even among people with genotype 1, African Americans are less likely to respond to treatment than whites.
Initial studies of pegylated interferon/ribavirin treatment did not enroll enough African Americans to draw meaningful conclusions about difference in response by race/ethnicity. However, three major trials specifically designed to compare treatment responses between whites and African Americans confirmed that treatment success rates* were about twice as high in whites (39-52%) vs. African Americans (19-26%), even when all study participants had genotype 1.
The reasons for African Americans’ decreased responsiveness to interferon-based treatment remain under investigation. Speculation centers on possible genetic differences that influence immune responses, since interferon is believed to operate in part by strengthening the immune system’s ability to fight hepatitis C. Some differences between whites and African Americans in patterns of immune response to hepatitis C have been described, though their relevance to treatment outcomes is not clear.
* Treatment success is defined as a sustained virologic response (SVR) – when hepatitis C remains undetectable 6 months after the end of treatment.
For references, click on the link below.
Estrada AL. Health disparities among African-American and Hispanic drug injectors--HIV, AIDS, hepatitis B virus and hepatitis C virus: a review. AIDS 2005 Oct;19 Suppl 3:S47-52. Abstract.
Armstrong GL, Simard EP, Wasley A, et al. The prevalence of hepatitis C virus (HCV) infection in the United States, 1999-2002. Program and abstracts of the 55th Annual Meeting of the American Association for the Study of Liver Diseases; October 29 - November 2, 2004; Boston, Massachusetts. 2004. Abstract 31. See abstract below.
Jeffers LJ, Cassidy W, Howell CD, et al. Peginterferon alfa-2a (40 kd) and ribavirin for black American patients with chronic HCV genotype 1. Hepatology. 2004 Jun;39(6):1702-8. Abstract.
Muir AJ, Bornstein JD, Killenberg PG, et al. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med. 2004 May 27;350(22):2265-71. Abstract.
Jacobson I, Brown R Jr, McCone J, et al. Weight based ribavirin dosing improves virologic response in HCV-infected genotype 1 African-Americans compared to flat dose ribavirin with peginterferon alfa-2b combination therapy. Program and abstracts of the 55th Annual Meeting of the American Association for the Study of Liver Diseases; October 29 - November 2, 2004; Boston, Massachusetts. Abstract 125. Abstract courtesy of HIVandHepatitis.com.
VIRAHEP-C (Viral Resistance to Antiviral Therapy of Chronic Hepatitis C): a research study examining differences and factors involved in response to treatment between whites and African Americans, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health.
Immune responses by race/ethnicity:
Sugimoto K, Stadanlick J, Ikeda F, et al. Influence of ethnicity in the outcome of hepatitis C virus infection and cellular immune response. Hepatology. 2003 Mar;37(3):590-9. Abstract.
Kaplan DE, Sugimoto K, Ikeda F, et al. T-cell response relative to genotype and ethnicity during antiviral therapy for chronic hepatitis C. Hepatology. 2005 Jun;41(6):1365-75. Abstract.
The Prevalence of Hepatitis C Virus (HCV) Infection in the United States, 1999-2002
Gregory L. Armstrong, Edgar P. Simard, Annemarie Wasley, Centers for Disease Control and Prevention, Atlanta, GA; Geraldine M. McQuillan, Centers for Disease Control and Prevention, Hyattsville, MD; Wendi L. Kuhnert, Miriam J. Alter, Centers for Disease Control and Prevention, Atlanta, GA.
Introduction: To examine trends in HCV prevalence, we analyzed data from the current, ongoing National Health and Nutrition Examination Survey (NHANES) conducted during 1999-2002 and compared prevalence with that from NHANES III, approximately 10 years earlier.
Methods: The civilian non-institutionalized population was surveyed using a multistage sampling design. Serum specimens were obtained from 15,079 participants aged 6 years and older and tested for anti-HCV by 3rd generation EIA (Ortho) and RIBA (Chiron). Specimens positive by RIBA were tested by quantitative and (if negative) qualitative RNA tests (Roche, 2nd version). Differences were considered statistically significant where p<0.05.
Results: The prevalence of anti-HCV was 1.6% (95% CI 1.3-1.9%), corresponding to 3.8 million positive persons, and was higher in males (2.1%) than females (1.1%) and higher among Blacks (3.0%) than Whites (1.5%) or Mexican Americans (1.3%). Prevalence was lowest among participants 6-29 years-old (0.4%) and highest among participants 45-49 years-old (7.1% among men, 2.3% among women). Among Black men in this age group 17.9% tested anti-HCV-positive. Of all anti-HCV positive persons, 69.9% were between age 35 and 54 years. Compared with NHANES III, the overall prevalence of anti-HCV was unchanged but peaked in an older age group (45-49 years in current NHANES vs. 35-39 years in NHANES III). Prevalence varied with several demographic and risk factors. Persons who had ever used injection drugs had a higher prevalence (57.3%) than those who had used non-injection drugs (3.5%) or those who had never used these drugs (0.7%). Prevalence increased with increasing numbers of lifetime sexual partners from 0.5% among persons with 0-1 lifetime partners to 1.0%, 4.7% and 12.1% among those with 2-9, 10-49 and 50+ partners, respectively. Prevalence was higher among those with a history of blood transfusion before 1990 (4.2%) than among those without (1.4%). Of the 148 anti-HCV positive specimens available for RNA testing, 82.4% were HCV RNA-positive, including 67.5% of specimens from persons under 40-years-old and 88.0% of those aged 40 years and older. Of all RNA-positive specimens, 68.0% had titers above 2M copies/ml. In RNA-positive specimens, ALT levels abnormal in 59.9%; 41.0% were 40-79 U/L and 18.9% were 80+ U/L. Among the RNA-positive participants, 63% stated that they had never been told they had “any kind of liver condition.”
Conclusions: The overall prevalence of HCV infection has not changed during the past 10 years but the peak in age-specific prevalence has shifted to older age groups, with very low prevalence in persons under 30 years old. Taken together, these data are consistent with a past epidemic of acute HCV infection, the result of which is a cohort of people, now aged 40-59 years, with a high prevalence of infection.