The key to the discovery of the Hepatitis D Virus (HDV) was the description in Turin, Italy in the mid-1970s of the
delta antigen and antibody in carriers of the
hepatitis B surface antigen. The new
antigen was first thought to be a marker of the Hepatitis B Virus (HBV) and in view of its intricate true nature, it would have possibly died away as another odd antigenic subtype of HBV, like many that were described in the 1970s. Fortunately, instead, a collaboration started in 1978 between the Turin group, and the National Institute of Health and Georgetown University in the US. With American facilities and expertise this collaboration led just a year later, in 1979, to the unfolding of an unexpected and amazing chapter in virology. Experiments in chimpanzees demonstrated that the
delta antigen was not a component of the HBV but of a separate defective virus requiring HBV for its
infection; it was named the hepatitis D virus to conform to the nomenclature of hepatitis viruses and classified within the genus Deltavirus. The animal experiments were also seminal in proposing to future clinical interpretation, the paradigm of a pathogenic
infection (
hepatitis D), that could develop only in HBV-infected patients, was mainly transmitted by
superinfection of HDV on chronic HBV carriers and had the ability to strongly inhibit the helper HBV. The discovery of the HDV has driven three directions of further research: (1) The understanding of the replicative and infectious mechanisms of the HDV. (2) The assessment of its epidemiological and medical impact. (3) The search for a
therapy for
chronic hepatitis D (CHD). This review summarizes the progress achieved in each field of research in the thirty years that have passed since the discovery of HDV.