The adventure of delta.

The hepatitis D virus (HDV) is unique in animal virology. It has a circular RNA genome that is the smallest of human viruses, requires the HBsAg capsid of the hepatitis B virus to assembly into infectious virions, parasitizes the transcriptional machinery of the host by hijacking cellular RNA polymerases to replicate its RNA genome and is replicated by a rolling circle mechanism unknown to mammalian cells. Hepatitis D is ubiquitous but prevalence varies throughout the world. It is the most severe form of chronic viral liver disorder; carriers of HBsAg superinfected by the HDV are the major victims and the reservoir of the infection. In the last 20 years vaccination against the hepatitis B virus (HBV) has decreased the circulation of HDV in industrialized countries; nevertheless hepatitis D is returning to Western Europe through immigration from HDV endemic areas. Hepatitis D is being rediscovered in the developing world. It has a significant medical impact on areas of Africa, Asia and South America where the partner HBV is not controlled; Pakistan and Mongolia appear to be worldwide the areas with the highest prevalence of the disease. A major obstacle in treatment is that the virus has no replicative function of its own to be targeted by antivirals. Peg-Interferon remains the mainstay of treatment. New strategies are explored to prevent entry of the virion into hepatocytes by blocking the cellular HBsAg receptor or preventing the prenylation process of the large-delta antigen necessary for the assembly of the HDV particle.