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-alpha therapy of chronic HBV-patients using the FNAB technique. Methods: Twenty chronic HBeAg+-patients were treated with pegylated a-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, IFN gamma 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(+) IFN gamma(+) 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-a therapy, and the antiviral effect may be mediated by both cytolytic and non-cytolytic mechanisms. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.