Immunomodulatory therapy for chronic hepatitis B virus infection

Hepatitis B virus (HBV) is one of the most prevalent viral pathogens of man with around 350 million chronically infected patients. It has been postulated that in persistently infected individuals the HBV-specific immune response is too weak to eliminate HBV from all infected hepatocytes, but sufficiently strong to continuously destroy HBV-infected hepatocytes and to induce chronic inflammatory liver disease. The primary aim in the treatment of chronic hepatitis B is to induce sustained disease remission and prevent serious complications like liver failure and/or hepatocellular carcinoma. The recent emergence of drug-resistant HBV mutants and post-treatment relapse as a consequence of nucleoside analogue monotherapy emphasizes that the principal goal should be to stimulate a successful immune response. In this paper we will focus on the immune response to HBV and we will review reported data on immunotherapeutic strategies like immunomodulatory drugs (cytokines and Thymic derivates) and vaccine therapies using currently available recombinant anti-HBV vaccines, lipopeptide-based T cell vaccine and newly developed genetic vaccines.