Translation of immunological knowledge into better treatments of chronic hepatitis B

The accumulating knowledge on the characteristics of the host immune response to HBV in convalescent subjects; patients with chronic hepatitis B, as well as during antiviral treatment suggests that immunotherapy approaches, aiming to induce strong and sustained HBV-specific T-cell reactivity, can be feasible and represent a promising strategy for successful treatment of patients with chronic hepatitis B. Several issues need to considered in designing such therapeutic protocols: 1. Combination regimens, involving an antiviral drug and an HBV vaccine, are likely to be more successful than monotherapy with either component and will be safer in patients with effective immune restoration (Fig. 1). 2. The timing of starting the vaccination, in a combined regimen with an antiviral drug plus a vaccine, should be planned according to the reduction of viral load and an adequate restoration of HBV-specific T cell response. 3. In order to achieve a sustained control of HBV replication the immunotherapy should aim to induce a coordinate activation of the different components of adaptive immunity, possibly with booster vaccinations depending on the response. 4. The end point is to achieve a balance in HBV-host interactions similar to the profile of subjects with resolution of acute HBV infection. In these subjects trace of HBV DNA usually persists [119] but the strong reactivity of virus-specific CD4+ and CD8+ T-cells controls the transcription and replication of the HBV genome without hepatic inflammation [6,120]. Finally, we have to bear in mind that chronic hepatitis B is a heterogeneous disease entity and adequate characterisation and selection of patients for therapeutic immunisation, according to HBV replication and virus-specific T-cell reactivity prior to therapy would be necessary and essential for the efficacy of this strategy.