Management of Delta Hepatitis 45 Years after the Discovery of HDV

In 1977 the viral Delta agent was discovered and subsequently characterized as the hepatitis Delta virus (HDV). HDV infection is associated with HBV infection since the defective HDV needs HBV to infect and replicate in the liver. Even if not a frequent cause of chronic liver disease, HDV infection is responsible for an aggressive progression of hepatitis towards advanced liver disease. At present, no FDA approved treatment exists for this specific form of hepatitis. Interferon alfa has been recommended as off-label therapy by major scientific societies (AASLD, EASL and APASL) and has proved effective in about one quarter of patients. In recent years, new therapeutic approaches have been studied, and EMA has approved a new drug (bulevirtide) for Delta hepatitis. In this review, we encompass the 45-year journey of managing Delta hepatitis and address the most recent developments in treating this severe and aggressive liver disease.