Hepatitis D (Delta)

The clue to the discovery of the hepatitis D virus was the description in Torino in the mid-1980s of the delta antigen in carriers of the hepatitis B surface antigen with chronic liver disease.

In view of its intricate nature and in the wake of the plethora of irrelevant hepatitis B virus (HBV) subtypes described at the time, the delta agent (HDV) would have probably been confused in the lot. Fortunately, in 1978 I had the privilege to continue research at the National Institute of Health (NIH) and at Georgetown University in the United States. The very initial transmission studies in chimpanzees raised the possibility that delta was a separate agent requiring help from HBV, not an antigen of HBV. With the expertise of the NIH, this hypothesis was rapidly confirmed, revealing at the end of the 1970s the existence of a new and unique human RNA virus. It resembles viroids of plants, possesses a ribozyme, and is the extreme of human parasitism, hijacking to its advantage the replicative machinery of the host.

HDV is pathogenic and causes the most aggressive forms of chronic viral hepatitis. Its impact extends worldwide, but is more ominous in the poorest countries of the developing world. The spread of HDV has diminished in the developed world with the expansion of HBV vaccination programs over the past 20 years. Though gratifying, the decline of HDV was nevertheless misleading; the perception that its infection was on the way to eradication has diminished alertness to hepatitis D. Though forgotten, HDV has not gone, but is returning to Western Europe with immigrants coming from regions where HDV remains endemic.

This issue of Seminars in Liver Disease reports on progress in the knowledge of the virology of HDV, of the epidemiological changes of its infection, and of the advances in the diagnosis and clinical perception of hepatitis D that have occurred since the discovery of the virus. It also addresses the current treatment efforts against a pathogen that remains a formidable challenge to therapy.

Finally, I wish to dedicate this issue to my mentor and friend, Professor Giorgio Verme, whose help and encouragement were essential to establish hepatitis D as a novel, distinct medical entity.