Abstract
Aim:
To investigate the anti-viral mechanism of combination therapy of interferon (IFN)-alpha and ribavirin in patients with chronic hepatitis B.
Methods:
Twenty patients were assigned to receive either IFN-alpha plus ribavirin (group A, n = 14) or no treatment as a control (group B, n = 6). Patients were analyzed for T-cell proliferative responses specific for hepatitis B virus (HBV)-antigen and cytokine production by peripheral blood mononuclear cells (PBMCs).
Results:
Combination therapy induced HBV-antigen specific CD4+ T-cell proliferative responses in four patients (28.6%). Production of high levels of HBV-specific IFN-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12 by PBMCs was found in five patients (35.7%), who showed significantly lower HBV DNA levels in serum at 12 mo after treatment ended (P = 0.038) and at 24 mo of follow-up (P = 0.004) than those without high levels of cytokine production.
Conclusion:
HBV-antigen specific CD4+ T cells may directly control HBV replication and secretion of anti-viral T helper 1 (Th1) cytokines by PBMCs during combination therapy of chronic hepatitis B with ribavirin and IFN-alpha.
MeSH terms
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Adult
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Aged
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Antiviral Agents / pharmacology
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Antiviral Agents / therapeutic use*
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CD4-Positive T-Lymphocytes / drug effects*
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CD4-Positive T-Lymphocytes / immunology
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Cell Proliferation / drug effects*
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Cytokines / blood*
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DNA, Viral / blood
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Drug Therapy, Combination
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Female
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Hepatitis B Antigens / immunology
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Hepatitis B virus / drug effects
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Hepatitis B virus / genetics
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Hepatitis B virus / immunology
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Hepatitis B, Chronic / drug therapy*
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Hepatitis B, Chronic / genetics
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Hepatitis B, Chronic / immunology
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Hepatitis B, Chronic / metabolism
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Humans
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Interferon alpha-2
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Interferon-alpha / pharmacology
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Interferon-alpha / therapeutic use*
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Interferon-gamma / blood
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Interleukin-12 / blood
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Lymphocyte Activation / drug effects*
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Male
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Middle Aged
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Prospective Studies
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Recombinant Proteins
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Ribavirin / pharmacology
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Ribavirin / therapeutic use*
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Th1 Cells / drug effects*
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Th1 Cells / metabolism
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Time Factors
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Treatment Outcome
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Tumor Necrosis Factor-alpha / blood
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Virus Replication / drug effects
Substances
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Antiviral Agents
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Cytokines
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DNA, Viral
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Hepatitis B Antigens
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Interferon alpha-2
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Interferon-alpha
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Interleukin-12
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Ribavirin
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Interferon-gamma