Intrahepatic CD8+ T-lymphocyte response is important for therapy-induced viral clearance in chronic hepatitis B infection

Background/Aims: To determine which immune cells contribute to HBV-clearance during antiviral therapy, we performed a longitudinal analysis of intrahepatic immune cells during interferon-α therapy of chronic HBV-patients using the FNAB technique. Methods: Twenty chronic HBeAg +-patients were treated with pegylated α-interferon combined with lamivudine or placebo for 52 weeks. FNAB and blood specimens were obtained at week 0, 2, 8 and 52. CD4+- and CD8+ T-lymphocytes, CD56+ cells, IFNγ and granzyme B (GrB) were immunocytochemically quantified. Results: The relative numbers of CD56 + cells and CD8+ T-lymphocytes were significantly higher in FNAB compared to blood at all time-points. Responders (n=9) exhibited significant increases in intrahepatic CD8+ and CD8 +GrB+ lymphocytes, a small elevation in CD8 +IFNγ+ T-lymphocytes, no change in CD4+ T-lymphocytes, and a decrease in intrahepatic CD56+ cells during the first weeks of therapy. In non-responders (n=11) no significant changes in CD4+- and CD8+ T-lymphocytes and an increase in intrahepatic and CD56+ cells were observed during therapy. Conclusions: The intrahepatic CD8+ T-lymphocyte, but not the CD4 + T-lymphocyte or NK/NKT-cell response, is important for HBV clearance during interferon-α therapy, and the antiviral effect may be mediated by both cytolytic and non-cytolytic mechanisms.

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