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Review
. 2021 Apr 16:13:461-468.
doi: 10.2147/JEP.S235550. eCollection 2021.

Experimental Drugs for the Treatment of Hepatitis D

Lisa Sandmann  1 , Markus Cornberg  1   2
Affiliations
Review

Experimental Drugs for the Treatment of Hepatitis D

Lisa Sandmann et al. J Exp Pharmacol. .

Abstract

Chronic hepatitis D virus infection is the most severe form of viral hepatitis. Antiviral treatment is urgently needed to prevent patients from developing end stage liver disease or hepatocellular carcinoma. Treatment options were limited to off-label use of pegylated interferon alfa until conditional approval of bulevirtide by the EMA (European Medicines Agency) in July 2020. However, several other antiviral compounds are currently investigated and represent promising agents for the treatment of chronic HDV infection.

Keywords: HBV/HDV coinfection; bulevirtide; hepatitis delta; interferon; lonafarnib.

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Conflict of interest statement

MC has received personal fees from AbbVie, Gilead Sciences, GSK, Janssen-Cilag, MSD Sharp & Dohme, Novartis, Spring Bank Pharmaceuticals, Swedish Orphan Biovitrum AB (SOBI). The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Therapeutic approaches for the treatment of chronic HDV infection are depicted in relation to the viral life cycle. (1) HDV virions attachment to heparan sulfate proteoglycans and binding of L-HBsAg pre-S1 region to the HBV/HDV specific receptor, hNTCP. Viral particles enter the cell through endocytosis and the viral ribonucleoprotein (RNP) is released in the cytoplasm. (2) Viral RNP translocation to the nucleus. (3) HDAg mRNA transcription and replication of HDV RNA. (4) L-HDAg contains a prenylation site that is farnesylated by a cellular farnesyltransferase before being re-translocated to the nucleus. (5) Both forms of HDAg interact with the newly synthesized genomic RNA to form new viral (RNP) that are exported to the cytoplasm. (6) Viral RNPs interact with the cytosolic part of HBsAg at the endoplasmic reticulum surface inducing their envelopment. (7) HDV virions are secreted form the infected cell. The different steps targeted by antiviral treatments are depicted. HBV co-infection is represented by presence of HBV cccDNA and integrated HBV DNA. The figure was created with BioRender.com.
See this image and copyright information in PMC

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