Background/Aims: To investigate whether dendritic cell changes are associated with the efficacy of interferon-alpha treatment we longitudinally analyzed circulating dendritic cells in children chronically infected with hepatitis B virus (HBV) undergoing interferon-alpha treatment. Methods:Thirty-one children with chronic hepatitis B (CHB) received interferon-a antiviral treatment for 52 weeks. Myeloid and plasmacytoid dendritic cell (pDCs) frequency and function were analyzed at weeks 0, 2, 12, 24, 36 and 52 in 22 CHB patients. Results:All patients exhibited an initially rapid decrease of circulating pDC numbers and CpG-induced endogenous interferon-a production within 2 weeks of interferon-a treatment. Subsequently, all responders displayed a continuous increase of both pDC numbers and function peaking around week 12. These responses were consequently accompanied by viral clearance, hepatitis B e antigen seroconversion, and the improvement of circulating myeloid dendritic cells and type I T helper cytokine levels. However, non-responders lacked these sequential responses compared with responders. Conclusions: pDCs may actively correlate with interferon-a therapy-induced viral clearance in pediatric patients with CHB. The recovery of blood pDC number and function may represent a prognostic marker for favourable response to interferon-a treatment in chronic hepatitis B. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.