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Pathogenesis, epidemiology, natural history, and clinical manifestations of hepatitis D virus infection

Francesco Negro, MD
Anna SF Lok, MD
Section Editor
Rafael Esteban, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Hepatitis D is caused by a defective virus: the hepatitis D virus (HDV). HDV is often referred to as hepatitis delta virus or delta agent. However, the term HDV is preferred.

HDV infection is closely associated with hepatitis B virus (HBV) infection. Although HDV can replicate autonomously [1], the simultaneous presence of HBV is required for complete virion assembly and secretion (see 'Virion structure' below). As a result, individuals with hepatitis D are always dually infected with HDV and HBV. Due to interference mechanisms that are not well understood, HBV replication is suppressed in most HDV-infected individuals.

This topic review will provide general information concerning the HDV structure and replication strategy, the nature of its strict association with HBV, and the epidemiology, pathogenesis, and clinical features of HDV infection. Issues related to diagnosis, treatment, prevention, and liver transplantation are discussed separately. (See "Diagnosis of hepatitis D virus infection" and "Treatment and prevention of hepatitis D virus infection".)


The HD virion comprises an RNA genome, a single HDV encoded antigen, and a lipoprotein envelope provided by HBV (figure 1).

HDV genome — The HDV genome is a small RNA molecule (1676 to 1683 nucleotides in size) bearing some structural analogies with plant viroids and virusoids [1]. HDV RNA is a single-stranded circle, with a high degree of self-complementarity and G+C content causing the circle to collapse as a rod-like structure [1]. Significant sequence heterogeneity (as high as 39 percent) exists among the different HDV isolates that have been sequenced, and a classification into eight HDV genotypes has been proposed [2].

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Literature review current through: Oct 2017. | This topic last updated: Jul 20, 2016.
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