Delta hepatitis: an update.

Hepatitis delta virus (HDV) is a unique defective RNA virus that requires the helper function of hepatitis B virus (HBV), which provides the essential coat protein for virion assembly and propagation. It is the smallest animal virus and the only one to possess a circular RNA genome, as seen in plant viruses. HDV has evolved into three major genotypes that differ in their geographic distribution. Infection with HDV has a worldwide distribution, although a dramatic decline in the incidence has been observed in the last decade in the Mediterranean area, likely as a result of HBV vaccination programs and improved socioeconomic conditions. HDV can be acquired either by coinfection with HBV or by superinfection of chronic HBsAg carriers. Whereas coinfection commonly resolves, superinfection progresses to chronicity in over 90% of the cases. Chronic hepatitis D is a severe and progressive disease leading to cirrhosis in about 70% of the cases. The pathogenesis of HDV-induced liver injury is still unknown. Regardless, dramatic advances have been made in the biology of HDV, as well as in the understanding of the complex interactions between HDV, HBV and the host. Currently, interferon-alfa at high doses is the only drug that can induce amelioration of the disease in about half the patients, but it has little effect on HDV viremia. Liver transplantation is the only valid therapeutic option for the treatment of end-stage HDV liver disease. Although the recent progress in molecular biology has dramatically advanced our knowledge of the biology of HDV, much remains to be understood in order to devise more effective therapies and vaccines for the control of this unique defective virus, which still remains a major cause of death or enlisting for liver transplantation.