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

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.

Figure 1

Abrogation of antigen-specific T-cell proliferative responses from patients 1-4 at 12 mo (^bP < 0.01 vs T cell and Anti CD8+).

Figure 2

Cytokine production levels in PBMCs in combination therapy patients. The vertical axis represents the ratio of the mean cytokine concentration of triplicate cultures obtained in the presence of antigen to that obtained without antigen. The numbers in the horizontal lines represent the patients. A: Th1 cytokine production in PBMCs in combination therapy patients; B: Th2 cytokine production in PBMCs in combination therapy patients.