This is a proposal for the Liver Center at BIDMC to act as a clinical trials center in a multicenter collaborative program to examine resistance to antiviral therapy in African Americans with hepatitis C. HCV is a common problem in the US with almost 4 million individuals exposed to the virus. HCV is the commonest cause of cirrhosis and liver cancer in the US. Almost 6% of African Americans have HCV and there response to Interferon based antiviral therapy is only 50% that of non-HIspanic whites. This study will examine the mechanism of viral resistance in African Americans to PEG-Interferon combined with ribavirin and examine the factors potentially responsible for viral resistance.
The specific Aims are to 1) Confirm that there is a difference in sustained viral clearance between AA and whites; 2) Identify factors that effect response to antiviral therapy; 3) determine the role of HCV viral kinetics during therapy on subsequent sustained viral clearance; 4) identify virological, immunological-and host genetic factors that determine viral clearance. Approximately 400 patients will be treated with PEG-IFN and ribavirin for 48 weeks and then followed for a further 48 weeks to determine sustained viral eradication. Pretreatment variables will be correlated with viral clearance. Specimens of liver tissue and serum will be collected for basic studies on viral resistance. These studies should help determine the best therapy for AA with HCV.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK060340-04
Application #
6765817
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (M1))
Program Officer
Robuck, Patricia R
Project Start
2001-08-21
Project End
2006-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
4
Fiscal Year
2004
Total Cost
$170,000
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Jin, Runyan; Cai, Ling; Tan, Ming et al. (2012) Optimum ribavirin exposure overcomes racial disparity in efficacy of peginterferon and ribavirin treatment for hepatitis C genotype 1. Am J Gastroenterol 107:1675-83
Howell, Charles D; Gorden, Alexis; Ryan, Kathleen A et al. (2012) Single nucleotide polymorphism upstream of interleukin 28B associated with phase 1 and phase 2 of early viral kinetics in patients infected with HCV genotype 1. J Hepatol 56:557-63
Golden-Mason, Lucy; Bambha, Kiran M; Cheng, Linling et al. (2011) Natural killer inhibitory receptor expression associated with treatment failure and interleukin-28B genotype in patients with chronic hepatitis C. Hepatology 54:1559-69
Evon, Donna M; Esserman, Denise A; Ramcharran, Darmendra et al. (2011) Social support and clinical outcomes during antiviral therapy for chronic hepatitis C. J Psychosom Res 71:349-56
Conjeevaram, Hari S; Wahed, Abdus S; Afdhal, Nezam et al. (2011) Changes in insulin sensitivity and body weight during and after peginterferon and ribavirin therapy for hepatitis C. Gastroenterology 140:469-77
Evon, Donna M; Ramcharran, Darmendra; Belle, Steven H et al. (2009) Prospective analysis of depression during peginterferon and ribavirin therapy of chronic hepatitis C: results of the Virahep-C study. Am J Gastroenterol 104:2949-58
Yee, L J; Im, K; Borg, B et al. (2009) Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus infection. Genes Immun 10:365-72
Hoofnagle, Jay H; Wahed, Abdus S; Brown Jr, Robert S et al. (2009) Early changes in hepatitis C virus (HCV) levels in response to peginterferon and ribavirin treatment in patients with chronic HCV genotype 1 infection. J Infect Dis 199:1112-20
Mengshol, J A; Golden-Mason, L; Castelblanco, N et al. (2009) Impaired plasmacytoid dendritic cell maturation and differential chemotaxis in chronic hepatitis C virus: associations with antiviral treatment outcomes. Gut 58:964-73
Dove, Lorna M; Rosen, Raymond C; Ramcharran, Darmendra et al. (2009) Decline in male sexual desire, function, and satisfaction during and after antiviral therapy for chronic hepatitis C. Gastroenterology 137:873-84, 884.e1

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