Hepatitis Delta virus: An overview


The History of Virus Discovery


From time to time highly severe (fulminant) hepatitis develops in patients with HBV infection. It has been demonstrated that fulminant HBV disease is associated predominantly with patient superinfection by new hepatitis D or hepatitis delta virus (HDV). HDV was first detected in patients with severe hepatitis B by M. Rizetto in 1977.


Classification and Structure of HDV


  • HDV is not included into any viral family (unclassified virus). It is placed into separate genus Deltavirus with single species hepatitis delta virus.
  • Hepatitis D virion is spherical particle with icosahedral symmetry, about 40 nm in size. Genome of HDV consists of very small circular negative single-stranded RNA, 1.7 kb in size. Genomic RNA encodes intrinsic HDV capsid antigen (HDAg or delta Ag).
  • No homology exists between HBV and HDV genomes. HDV is a defected satellite virus (subviral agent) that reproduces only in presence of helper hepatitis B virus.
  • HDV requires HBsAg of hepatitis B virus – together with host cell lipids HBsAg creates envelope for HDV virion.

Viral Replication Cycle


  • HDV exploits the same membrane receptor as HBV (liver bile acid transporter protein or LBAT) to infect hepatocytes. After uncoating HDV nucleocapsid is transported into the cell nucleus, where genome replication occurs.
  • HDV uses cellular RNA polymerases to create circular genomic RNA and linear mRNA for translation of protein HDAg.
  • HDAg binds to viral genomic RNA transported into cytoplasm resulting in nucleocapsid formation. It acquires external coat from proteins of HBsAg of hepatitis B virus and releases via cytoplasmic membrane of hepatocytes.
  • Thus, productive HDV infection is possible only in case of hepatocyte co-infection with HDV and HBV agents.

Characteristics of HDV Infection


  • About 15-20 mln people are currently coinfected with HDV and HBV worldwide. HDV infection is often associated with the most severe forms of hepatitis in HBsAg-positive patients. Chronically infected individuals demonstrate high risk of progression to end-stage liver disease, resulting in cirrhosis and hepatic carcinoma.
  • Intravenous drug abusers and persons, who received multiple hemotransfusions, are of high risk of HDV infection.
  • The primary routes of transmission for HDV are similar to HBV, though HDV is not a sexually transmitted disease. Perinatal transmission of HDV is rare.
  • The incubation period varies from 2 to 12 weeks.
  • While HDV is absolutely dependent on a coexistent HBV infection, acute hepatitis D may develop either as a simultaneous infection (coinfection) with HBV or as a superinfection of patient with primary chronic HBV infection.
  • Coinfection is similar to acute hepatitis B resulting in viral elimination in more than 90% of cases with complete recovery.
  • By contrast, superinfection by HDV is frequently associated with severe acute (“fulminant”) hepatitis that, if recovered, results in chronic HDV disease (near 90% of cases). Fulminant hepatitis D is a life-threatening disorder with fatality of 70-90%.

Laboratory Diagnosis


  • Serological tests are used for hepatitis D diagnosis. Both HDAg and anti-delta IgM antibodies are determined by ELISA in case of acute delta infection. Also HDV RNA is discovered in patient’s serum by PCR.
  • All markers of HDV replication decline to convalescence, but HDV antibodies may disappear within months or years.

Treatment and Prophylaxis of hepatitis D


  • Recombinant interferon-alpha is commonly used for treatment of delta hepatitis. Antiviral chemotherapy of HDV infection is currently not elaborated.
  • In healthy individuals delta hepatitis can be fully prevented by vaccination of persons with hepatitis В vaccine. However, vaccination doesn’t protect chronic hepatitis В carriers from superinfection by HDV.