VIRAHEP-C Clinical Center

Summary

Principal Investigator: A S F Lok
Abstract: Chronic hepatitis C is the leading cause of chronic liver disease and cirrhosis in the United States and is now the leading cause for liver transplantation due to end-stage liver disease. Approximately 1.8% of population (4 million) in the United States have antibody to hepatitis C virus (anti-HCV) and approximately 2.7 million Americans have evidence of chronic infection. The prevalence of antibody to HCV is higher among African Americans (3.2%) than among the non-Hispanic whites (1.8%). Treatment of chronic hepatitis C remains problematical and unsatisfactory. Interferon (IFN) monotherapy given as three times weekly injections has been shown to have biochemical, virological and histological beneficial effects. However, sustained virological response (SVR) is seen in only a minority of patients (6-16%). Treatment with combination of IFN + and ribavirin for 24 or 48 weeks results in SVR rates of up to 35 to 43% respectively. Very limited published data is currently available on the impact of race on response to antiviral therapy in patients with chronic hepatitis C. Most available reports show that African Americans have a significantly lower SVR when compared to non-Hispanic whites with all treatment regimens. We are proposing a multicenter, controlled clinical trial of combination therapy of pegylated interferon + ribavirin for African Americans and non-Hispanic whites chronically infected with HCV genotype 1 virus. Treatment will be administered for a total duration of 48 weeks with a 48-week follow-up post completion of therapy. A total of 400 patients with equal numbers of Caucasians and African Americans (200 in each group) will be enrolled into this study. The primary end-point of this trial is to determine rate of SVR among African Americans and non-Hispanic whites. In addition, factors predictive for a favorable response and patterns of virological response will also be assessed in the two racial groups. The objectives of this trial are to evaluate: (a) the rates of SVR among African Americans and non-Hispanic Whites with chronic hepatitis C after treatment with combination therapy using pegylated interferon and ribavirin for 48 weeks; (b) the factors that are predictive of a SVR to combination therapy in each of the two racial groups and factors associated with poorer response in African Americans and (c) the patterns of virological response (including viral kinetics) early during treatment and determine if different responses predict the ultimate outcome (sustained response, relapse or a lack of response) in each of the two racial groups. The findings of this study will allow us to develop specific algorithms to predict rates of SVR to therapy among African Americans based on their pre-treatment characteristics and patterns of virological response during therapy.
Funding Period: 2001-09-01 - 2008-07-31
more information: NIH RePORT

Top Publications

  1. ncbi Early changes in hepatitis C virus (HCV) levels in response to peginterferon and ribavirin treatment in patients with chronic HCV genotype 1 infection
    Jay H Hoofnagle
    Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda 20817, USA
    J Infect Dis 199:1112-20. 2009
  2. pmc Host genetics, steatosis and insulin resistance among African Americans and Caucasian Americans with hepatitis C virus genotype-1 infection
    A Danielle Iuliano
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Intervirology 52:49-56. 2009
  3. pmc Optimum ribavirin exposure overcomes racial disparity in efficacy of peginterferon and ribavirin treatment for hepatitis C genotype 1
    Runyan Jin
    School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA
    Am J Gastroenterol 107:1675-83. 2012
  4. pmc A novel unsupervised method to identify genes important in the anti-viral response: application to interferon/ribavirin in hepatitis C patients
    Leonid I Brodsky
    Institute of Evolution, University of Haifa, Haifa, Israel
    PLoS ONE 2:e584. 2007
  5. pmc Social support and clinical outcomes during antiviral therapy for chronic hepatitis C
    Donna M Evon
    Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC 27599, United States
    J Psychosom Res 71:349-56. 2011
  6. ncbi Changes in insulin sensitivity and body weight during and after peginterferon and ribavirin therapy for hepatitis C
    Hari S Conjeevaram
    Division of Gastroenterology, The University of Michigan, 3912 Taubman Center, 1500 East Medical Center Dr, Ann Arbor, Michigan 48109, USA
    Gastroenterology 140:469-77. 2011
  7. pmc 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
    Charles D Howell
    University of Maryland School of Medicine, Program in Genetics and Genomic Medicine, Baltimore, MD, USA
    J Hepatol 56:557-63. 2012
  8. pmc Fibrosis progression in African Americans and Caucasian Americans with chronic hepatitis C
    Norah A Terrault
    Department of Medicine, University of California San Francisco, San Francisco, California 94143 0538, USA
    Clin Gastroenterol Hepatol 6:1403-11. 2008
  9. pmc Impaired plasmacytoid dendritic cell maturation and differential chemotaxis in chronic hepatitis C virus: associations with antiviral treatment outcomes
    J A Mengshol
    Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado Denver, Colorado, USA
    Gut 58:964-73. 2009
  10. pmc Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus infection
    L J Yee
    Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Genes Immun 10:365-72. 2009

Scientific Experts

  • Leland J Yee
  • D M Evon
  • HUGO RAMON ROSEN
  • Charles Howell
  • Jay H Hoofnagle
  • Milton W Taylor
  • Ermei Yao
  • R J Fontana
  • N A Terrault
  • Hari S Conjeevaram
  • Abdus S Wahed
  • Nezam Afdhal
  • Robert S Brown
  • Steven H Belle
  • David E Kleiner
  • Jared Klarquist
  • James R Burton
  • John E Tavis
  • Steven Zacks
  • Lennox J Jeffers
  • Michael W Fried
  • Stephanie Straley
  • Huiying Yang
  • George Tang
  • Yuling Wei
  • Nathan Cannon
  • Abdus Wahed
  • Sherry Kelsey
  • Thelma E Wiley
  • T Jake Liang
  • Sharon Lawlor
  • Lorna Dove
  • Carol Hermitt
  • Adrian Di Bisceglie
  • Dai Wang
  • Scott Weston
  • Jennifer Cline
  • James Everhart
  • Tiffany Geahigan
  • Leonard B Seeff
  • Shana Stovel
  • Karen Dougherty
  • Donna Harsh
  • Dickens Theodore
  • Maureen Donlin
  • Melissa Hinds
  • Roshan Shrestha
  • Ping Wang
  • Richard A Bilonick
  • Stephen B Thomas
  • Shirley Brown
  • Eliana Agudelo
  • Edward Doo
  • Maria deMedina
  • Laurie Koozer
  • Karen Callison
  • Marika Haritos
  • Monique Williams
  • KyungAh Im
  • Geoffrey Block
  • Corneliu Sanda
  • Stephanie Kelley
  • Scott R Smith
  • Patricia Robuck
  • Paris Davis
  • Mary Ferris
  • Lucy Golden-Mason
  • Takuma Tsukahara
  • Runyan Jin
  • Lorna M Dove
  • A Danielle Iuliano
  • J A Mengshol
  • Shvawn McPherson Baker
  • Darmendra Ramcharran
  • K A Im
  • Xiaowen Su
  • Kelly Gibson
  • Maria Martin
  • Jane Lewis
  • S L Rhodes
  • Song Zhang
  • Jake Heberlein
  • Leonid I Brodsky
  • Ling Cai
  • John G McHutchison
  • Thomas C Dowling
  • Ming Tan
  • James E Everhart
  • Joseph Zmuda
  • Eleanor Feingold

Detail Information

Publications25

  1. ncbi Early changes in hepatitis C virus (HCV) levels in response to peginterferon and ribavirin treatment in patients with chronic HCV genotype 1 infection
    Jay H Hoofnagle
    Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda 20817, USA
    J Infect Dis 199:1112-20. 2009
    ..Trial registration. ClinicalTrials.gov identifier: NCT00038974 ...
  2. pmc Host genetics, steatosis and insulin resistance among African Americans and Caucasian Americans with hepatitis C virus genotype-1 infection
    A Danielle Iuliano
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Intervirology 52:49-56. 2009
    ..These results could imply that some IL10,LEPR and TGF-beta1 polymorphisms may modify an association between steatosis and IR...
  3. pmc Optimum ribavirin exposure overcomes racial disparity in efficacy of peginterferon and ribavirin treatment for hepatitis C genotype 1
    Runyan Jin
    School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA
    Am J Gastroenterol 107:1675-83. 2012
    ....
  4. pmc A novel unsupervised method to identify genes important in the anti-viral response: application to interferon/ribavirin in hepatitis C patients
    Leonid I Brodsky
    Institute of Evolution, University of Haifa, Haifa, Israel
    PLoS ONE 2:e584. 2007
    ..Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging...
  5. pmc Social support and clinical outcomes during antiviral therapy for chronic hepatitis C
    Donna M Evon
    Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC 27599, United States
    J Psychosom Res 71:349-56. 2011
    ..To determine if social support (SS) is associated with clinical outcomes during antiviral therapy for chronic hepatitis C virus (HCV)...
  6. ncbi Changes in insulin sensitivity and body weight during and after peginterferon and ribavirin therapy for hepatitis C
    Hari S Conjeevaram
    Division of Gastroenterology, The University of Michigan, 3912 Taubman Center, 1500 East Medical Center Dr, Ann Arbor, Michigan 48109, USA
    Gastroenterology 140:469-77. 2011
    ..The effect of antiviral treatment on insulin sensitivity is not well-known. We evaluated changes in insulin resistance and weight in patients with hepatitis C during and after peginterferon and ribavirin therapy...
  7. pmc 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
    Charles D Howell
    University of Maryland School of Medicine, Program in Genetics and Genomic Medicine, Baltimore, MD, USA
    J Hepatol 56:557-63. 2012
    ..We studied the relationship between IL28B gene-related SNP rs12979860 and early viral kinetics (day 0-28) during peginterferon and ribavirin treatment, in 173 African Americans (AA) and 188 Caucasian Americans (CA) with HCV genotype 1...
  8. pmc Fibrosis progression in African Americans and Caucasian Americans with chronic hepatitis C
    Norah A Terrault
    Department of Medicine, University of California San Francisco, San Francisco, California 94143 0538, USA
    Clin Gastroenterol Hepatol 6:1403-11. 2008
    ..Prior studies suggest the rate of liver fibrosis progression is slower in African Americans (AAs) than Caucasian Americans (CAs) with chronic HCV infection...
  9. pmc Impaired plasmacytoid dendritic cell maturation and differential chemotaxis in chronic hepatitis C virus: associations with antiviral treatment outcomes
    J A Mengshol
    Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado Denver, Colorado, USA
    Gut 58:964-73. 2009
    ..Studies to date have produced inconsistent results regarding DC maturation and function: no large study has examined DCs before and after therapy...
  10. pmc Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus infection
    L J Yee
    Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Genes Immun 10:365-72. 2009
    ..Our findings provide additional support for the potential importance of genetic variation in the IL-6 gene and the response to HCV therapy...
  11. ncbi Decline in male sexual desire, function, and satisfaction during and after antiviral therapy for chronic hepatitis C
    Lorna M Dove
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, New York Presbyterian Medical Center, New York, New York, USA
    Gastroenterology 137:873-84, 884.e1. 2009
    ..The recommended therapy for chronic hepatitis C, pegylated interferon and ribavirin for 24 or 48 weeks, has many known adverse side effects. The aim of this study was to evaluate the impact of antiviral therapy on male sexual health...
  12. ncbi Prospective analysis of depression during peginterferon and ribavirin therapy of chronic hepatitis C: results of the Virahep-C study
    Donna M Evon
    Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, North Carolina 27599, USA
    Am J Gastroenterol 104:2949-58. 2009
    ..The objectives of this study were to determine the association between patient characteristics and depression before and during treatment and to evaluate the relationship between depression and treatment outcomes...
  13. pmc Polymorphism in the human major histocompatibility complex and early viral decline during treatment of chronic hepatitis C
    Leland J Yee
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA
    Antimicrob Agents Chemother 53:615-21. 2009
    ..018), in CA carriers for Cw*03 (2.99; P = 0.046), and in CA noncarriers for DQA1*04 (2.66; P = 0.018) or DQB1*0402 (2.65; P = 0.018). MHC alleles are associated with the viral decline during the first 28 days of peginterferon therapy...
  14. ncbi Prospective analysis of effector and regulatory CD4+ T cells in chronic HCV patients undergoing combination antiviral therapy
    James R Burton
    University of Colorado Denver, School of Medicine, Division Gastroenterology and Hepatology, Hepatitis C Research Center, Aurora, CO 80045, USA
    J Hepatol 49:329-38. 2008
    ..The role of HCV-specific CD4(+) T cells and regulatory T cells in influencing the outcome of antiviral therapy is incompletely defined...
  15. ncbi Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1
    Hari S Conjeevaram
    Division of Gastroenterology, The University of Michigan, Ann Arbor, Michigan 48109 0362, USA
    Gastroenterology 131:470-7. 2006
    ..Compared with Caucasian Americans (CA), African Americans (AA) with chronic hepatitis C are less likely to respond to interferon-based antiviral therapy...
  16. ncbi Modeling hepatic fibrosis in African American and Caucasian American patients with chronic hepatitis C virus infection
    Robert J Fontana
    Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
    Hepatology 44:925-35. 2006
    ..The excellent performance of the Virahep-C model in an external validation cohort suggests the findings are replicable and potentially generalizable...
  17. ncbi Race, insulin resistance and hepatic steatosis in chronic hepatitis C
    Hari S Conjeevaram
    Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109 0362, USA
    Hepatology 45:80-7. 2007
    ..32-0.91, P = 0.02). Insulin resistance but not steatosis was associated with a lower rate of sustained virological response when adjusted for known factors that predict response (relative risk 0.87, 95% CI 0.77-0.99, P = 0.028)...
  18. pmc Changes in gene expression during pegylated interferon and ribavirin therapy of chronic hepatitis C virus distinguish responders from nonresponders to antiviral therapy
    Milton W Taylor
    Department of Biology, Indiana University, Bloomington, IN 47401, USA
    J Virol 81:3391-401. 2007
    ..No specific regulatory gene could be identified as responsible for this global blunting or the racial differences...
  19. ncbi Myxovirus-1 and protein kinase haplotypes and fibrosis in chronic hepatitis C virus
    Leland J Yee
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Hepatology 46:74-83. 2007
    ..Although we observed a similar protective trend for the Mx1-CAGT haplotype in the validation set, the association was not statistically significant...
  20. ncbi Selective decrease in hepatitis C virus-specific immunity among African Americans and outcome of antiviral therapy
    Hugo R Rosen
    Integrated Program in Immunology and Hepatitis C Research Center, Division of Gastroenterology and Hepatology, University of Colorado, Denver, CO, USA
    Hepatology 46:350-8. 2007
    ..007). ELISPOT response was independently associated with SVR by multivariable analysis...
  21. ncbi Cutting edge: programmed death-1 expression is increased on immunocytes in chronic hepatitis C virus and predicts failure of response to antiviral therapy: race-dependent differences
    Lucy Golden-Mason
    Division of Gastroenterology and Hepatology, Hepatitis C Center, University of Colorado Health Sciences Center and National Jewish Hospital, Aurora, CO 80045, USA
    J Immunol 180:3637-41. 2008
    ..Collectively, these data indicate that PD-1 is critical in persistent HCV and successful therapy results in global down-regulation of its expression...
  22. pmc Peginterferon pharmacokinetics in African American and Caucasian American patients with hepatitis C virus genotype 1 infection
    Charles D Howell
    University of Maryland Baltimore School of Medicine, Baltimore, Maryland 21201, USA
    Clin Gastroenterol Hepatol 6:575-83. 2008
    ....
  23. pmc Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection
    S L Rhodes
    Cedars Sinai Medical Center, Los Angeles, CA, USA
    Genes Immun 9:328-33. 2008
    ..In this regard, future studies examining broader patient populations are warranted...
  24. pmc Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C
    Xiaowen Su
    Medical Genetics Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
    J Hepatol 49:184-91. 2008
    ..We studied single nucleotide polymorphisms (SNPs) in IPGs and ISGs for their associations with response to pegylated interferon alpha-2a (Peg-IFN-alpha) plus ribavirin therapy in HCV genotype-1 infected patients...
  25. pmc A general method for nested RT-PCR amplification and sequencing the complete HCV genotype 1 open reading frame
    Ermei Yao
    Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri 63104, USA
    Virol J 2:88. 2005
    ..This places divergent demands of the amplification conditions that can be very difficult to reconcile...