Transient restoration of anti-viral T cell responses induced by lamivudine therapy in chronic hepatitis B

J Hepatol. 2003 Oct;39(4):595-605. doi: 10.1016/s0168-8278(03)00292-7.


Background/aims: Lamivudine therapy in patients with chronic hepatitis B can induce the recovery of antiviral T cell responses. It is unknown whether the recovery of T cell responsiveness is long-lasting and persists throughout the treatment and whether the elevation of viremia which follows therapy withdrawal can restore a condition of T cell unresponsiveness.

Methods: Frequency and function of circulating hepatitis B virus (HBV)-specific CD4 and CD8 cells from 12 hepatitis e surface antigen + patients with chronic hepatitis B were studied longitudinally before, during and after lamivudine therapy by intracellular cytokine staining, proliferation and cytotoxicity assays against HBV proteins and peptides. CD4-mediated responses were analyzed in all patients, whereas CD8 cells were studied in 6 HLA-A2+ patients.

Results: HBV-specific CD4 and CD8 reactivity showed a bi-phasic behavior under lamivudine therapy with an early enhancement of T cell frequency and intensity of responses followed by a persistent decline starting from the 5th to 6th month of treatment.

Conclusions: Since restoration of HBV-specific T cell reactivity is only transient, our study indicates that therapeutic stimulation of HBV-specific T cell responses to complement lamivudine treatment should be done early after the initiation of lamivudine. Moreover, the transient nature of the immune reconstitution may represent a favorable condition for virus reactivation once lamivudine therapy is withdrawn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Division / drug effects
  • Female
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Mitogens / pharmacology
  • Phytohemagglutinins / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • Tetanus Toxoid / pharmacology
  • Time Factors


  • Mitogens
  • Phytohemagglutinins
  • Reverse Transcriptase Inhibitors
  • Tetanus Toxoid
  • Lamivudine