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. 2019 Jun 23;7(4):231-245.
doi: 10.1093/gastro/goz023. eCollection 2019 Aug.

Hepatitis D infection: from initial discovery to current investigational therapies

Ben L Da  1 , Theo Heller  2 , Christopher Koh  2
Affiliations

Hepatitis D infection: from initial discovery to current investigational therapies

Ben L Da et al. Gastroenterol Rep (Oxf). .

Abstract

Hepatitis D is the most severe form of viral hepatitis associated with a more rapid progression to cirrhosis and an increased risk of hepatocellular carcinoma and mortality compared with hepatitis B mono-infection. Although once thought of as a disappearing disease, hepatitis D is now becoming recognized as a serious worldwide issue due to improvement in diagnostic testing and immigration from endemic countries. Despite these concerns, there is currently only one accepted medical therapy (pegylated-interferon-α) for the treatment of hepatitis D with less than desirable efficacy and significant side effects. Due to these reasons, many patients never undergo treatment. However, increasing knowledge about the virus and its life cycle has led to the clinical development of multiple promising new therapies that hope to alter the natural history of this disease and improve patient outcome. In this article, we will review the literature from discovery to the current investigational therapies.

Keywords: Hepatitis D; epidemiology; hepatitis B; natural history; novel therapies; outcome; treatment.

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Figures

Figure 1.
Figure 1.
Hepatitis D virus viral life cycle and sites of drug target. 1. Hepatitis D virus (HDV) virion attaches to the hepatocyte via interaction between hepatitis B surface antigen proteins and the sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter. 2. HDV ribonucleoprotein (RNP) is translocated to nucleus mediated by the hepatitis D antigen (HDAg). 3. HDV genome replication occurs via a ‘rolling-circle’ mechanism. 4. HDV antigenome is transported out of the nucleus to the endoplasmic reticulum (ER). 5. HDV antigenome is translated in the ER into small HDAg (S-HDAg) and large HDAg (L-HDAg). 6. L-HDAg undergoes prenylation prior to assembly. 7. S-HDAg is transported back to the nucleus where it supports HDV replication. 8. New HDAg molecules are associated with new transcripts of genomic RNA to form new RNPs that are exported to the cytoplasm. 9. New HDV RNP associates with hepatitis B virus (HBV) envelop proteins and assembled into HDV virions. 10. Completed HDV virions are released from the hepatocyte via the trans-Golgi network.
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