T-cell response relative to genotype and ethnicity during antiviral therapy for chronic hepatitis C

Authors

  • David E. Kaplan,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia
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  • Kazushi Sugimoto,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia
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  • Fusao Ikeda,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia
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  • Jason Stadanlick,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia
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  • Mary Valiga,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia
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  • Kirti Shetty,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia
    2. Division of Gastroenterology, Department of Medicine, Philadelphia VA Medical Center, Philadelphia, PA
    3. Division of Gastroenterology, Department of Medicine, Georgetown University, Washington, DC
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  • K. Rajender Reddy,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia
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  • Kyong-Mi Chang

    Corresponding author
    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia
    2. Division of Gastroenterology, Department of Medicine, Philadelphia VA Medical Center, Philadelphia, PA
    • Division of Gastroenterology, Department of Medicine, University of Pennsylvania & Philadelphia VAMC, A212 Medical Research, Philadelphia VAMC, University and Woodland Avenues, Philadelphia, PA 19104
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    • fax: 215-823-4394


  • Potential conflict of interest: Nothing to report.

Abstract

Viral genotype and host ethnicity are important predictors of viral clearance during antiviral therapy for chronic hepatitis C virus (HCV) infection. Based on the role of T cells in natural HCV clearance, we hypothesized that T cells may contribute to the genotypic and ethnic difference in treatment outcome. To test this hypothesis, T-cell response to HCV antigens (core, nonstructural NS3/4 and NS5) and control phytohemagglutinin (PHA) was monitored prospectively and was correlated with virological outcome in 41 patients chronically infected with HCV (27 genotype 1, 14 genotype 2 or 3; 19 black persons, 22 white persons) undergoing combined interferon alfa and ribavirin therapy. Interestingly, in patients with genotype 2 or 3 infection, enhanced virological response coincided with a greater T-cell response to HCV NS3/4 antigen at baseline (50% vs. 15%; P = .026) that augmented further during therapy (29% vs. 4%; P = .035) compared with genotype 1-infected patients. However, HCV-specific T-cell response remained weak in genotype 1-infected patients regardless of virological outcome or ethnicity. Furthermore, virological outcome was associated with a suppressed baseline proliferative response to phytohemagglutinin (P < .03) that increased during therapy (P < .003) independent of ethnicity or genotype. In conclusion, HCV-specific T-cell response was associated with HCV genotype but not with therapeutic clearance of HCV infection. The association between treatment outcome and phytohemagglutinin response suggests more global and antigen-nonspecific mechanisms for therapeutic HCV clearance. (HEPATOLOGY 2005;41:1365–1375.)

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