D Is for Delta: A Primer on Hepatitis D Virus

Rowen K. Zetterman, MD


July 02, 2013

In This Article

The Identification of Hepatitis D Virus

Hepatitis D virus (HDV) was identified in the 1970s in the hepatocyte nuclei of patients with chronic hepatitis B virus (HBV) disease.[1] HDV was observed in patients with more severe liver disease and was found only in patients infected with HBV. Initially thought to be a part of HBV, it was given the name "delta antigen" and was associated with development of a distinct anti-delta antibody. Delta antigen was subsequently determined to be an RNA virus covered by HBV surface antigens,[2] a distinct hepatotrophic virus occurring in patients in conjunction with HBV infection.

Hepatitis D Virology

HDV is an RNA virus circulating as a spherical particle with an RNA core and a capsid of small, medium, and large HBV envelope proteins (surface antigen).[3] HDV is composed of 1700 nucleotides in a single-stranded circular form[4] and is the only member of the deltavirus genus identified to date.

HDV is the smallest known animal virus and is a defective virus more related to plant viruses than to animal viruses.[5] It replicates only within the liver, where it encodes for a single protein, hepatitis D antigen (HDAg), which exists in 2 isoforms as small and large HDAg.[3] HDV does not require HBV proteins to replicate within a host cell, but uses host RNA polymerases and RNA-editing enzyme to complete its life cycle.[6] HDAg is the only protein expressed by the virus.

Eight genotypes of HDV have been identified[7]:

Genotype 1 is distributed worldwide, including the Western Hemisphere;

Genotype 2 is found in Eastern Asia and Russia;

Genotype 3 is found in South America in the Amazon basin;

Genotype 4 is largely found in Japan and China; and

The remaining genotypes are present in Africa.

Patients with repeated exposure to HDV can have more than 1 circulating genotype. As a defective RNA virus requiring concurrent HBV infection to provide its virion coat of HBV envelope proteins, HDV infection will occur either as simultaneous coinfection with both viruses or as superinfection of a hepatitis B carrier from a person carrying both HBV and HDV.

Epidemiology of Hepatitis D Infection

HDV is endemic worldwide, and all age groups are affected.[8] Humans are the natural reservoir for HDV, with approximately 15,000,000 persons infected worldwide.[9] HDV is highly endemic in Eastern Europe, parts of Africa and the Middle East, and the Amazon basin, whereas prevalence is low in northern Europe and the United States.

The prevalence of HDV has been declining in the developed world,[10] possibly because of hepatitis B vaccination and improved public health standards, blood product screening, and HIV care. In the 1980s, HDV was found in 7% of HBV carriers without, and 24% of HBV carriers with, liver disease. By 1997, only 8% of HBV carriers with liver disease were found to be concurrently infected with HDV. Although the prevalence of HDV has fallen in some developed regions, increased immigration of people from highly endemic regions has resulted in the continuing presence of HDV in many countries.[11]


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