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Hepatitis C virus (HCV) readily sets up a persistent infection and is a major cause of liver disease worldwide. Interferon alfa and ribavirin therapy lead to sustained clearance of virus in 31% to 64% of patients with type 1 and non-type 1 genotypes, respectively. It is not clear to what extent these drugs act directly to reduce HCV replication, or indirectly via host immune responses, and what evoked immune responses are associated with clinical outcome. We have examined prospectively 15 patients with chronic HCV infection before, during, and after combination therapy. Quantitative assays for HCV antigen-specific CD4+ and CD8+ T-cell responses, and flow cytometric assays for analysis of the phenotype of T cells, in addition to viral sequencing of core protein, were performed throughout the treatment and follow-up period over 18 months. We found enhancement of proliferative T-cell responses during therapy. Proliferative responses are strikingly heterogeneous in terms of specificity, kinetics, and magnitude. Proliferative responses are often not associated with interferon-gamma release. T-cell responses are rarely sustained irrespective of treatment outcome and this is not due to the evolution of new immune escape variants. T-cell responses tend to peak late in the course of treatment. In conclusion, combination therapy for HCV has a transient effect on host virus-specific T cells in the blood. Induction of sustained T-cell responses may require additional immune modulation later in therapy.

Original publication

DOI

10.1053/jhep.2002.35344

Type

Journal article

Journal

Hepatology (Baltimore, Md.)

Publication Date

09/2002

Volume

36

Pages

743 - 754

Addresses

Centre for Hepatology, Royal Free Hospital, London; and the Nuffield Department of Medicine, Oxford University, Oxford, UK. ellie.barnes@ntlworld.com

Keywords

CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Humans, Hepatitis C, Chronic, Viral Core Proteins, Hepatitis C Antigens, Antiviral Agents, CD4-CD8 Ratio, Drug Therapy, Combination, Cohort Studies, Prospective Studies, Cell Division, Amino Acid Sequence, Mutation, Molecular Sequence Data, Adult, Middle Aged, Female, Male, Interferon-gamma, Biological Evolution