Ribavirin and IFN-alpha combination therapy induces CD4+ T-cell proliferation and Th1 cytokine secretion in patients with chronic hepatitis B

World J Gastroenterol. 2007 Nov 7;13(41):5440-5. doi: 10.3748/wjg.v13.i41.5440.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Proliferation / drug effects*
  • Cytokines / blood*
  • DNA, Viral / blood
  • Drug Therapy, Combination
  • Female
  • Hepatitis B Antigens / immunology
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / metabolism
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Interferon-gamma / blood
  • Interleukin-12 / blood
  • Lymphocyte Activation / drug effects*
  • Male
  • Middle Aged
  • Prospective Studies
  • Recombinant Proteins
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use*
  • Th1 Cells / drug effects*
  • Th1 Cells / metabolism
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Cytokines
  • DNA, Viral
  • Hepatitis B Antigens
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Ribavirin
  • Interferon-gamma