Medical Advances in Hepatitis D Therapy: Molecular Targets

Int J Mol Sci. 2022 Sep 16;23(18):10817. doi: 10.3390/ijms231810817.


An approximate number of 250 million people worldwide are chronically infected with hepatitis B virus, making them susceptible to a coinfection with hepatitis D virus. The superinfection causes the most severe form of a viral hepatitis and thus drastically worsens the course of the disease. Until recently, the only available therapy consisted of interferon-α, only eligible for a minority of patients. In July 2020, the EMA granted Hepcludex conditional marketing authorization throughout the European Union. This first-in-class entry inhibitor offers the promise to prevent the spread in order to gain control and eventually participate in curing hepatitis B and D. Hepcludex is an example of how understanding the viral lifecycle can give rise to new therapy options. Sodium taurocholate co-transporting polypeptide, the virus receptor and the target of Hepcludex, and other targets of hepatitis D therapy currently researched are reviewed in this work. Farnesyltransferase inhibitors such as Lonafarnib, targeting another essential molecule in the HDV life cycle, represent a promising target for hepatitis D therapy. Farnesyltransferase attaches a farnesyl (isoprenyl) group to proteins carrying a C-terminal Ca1a2X (C: cysteine, a: aliphatic amino acid, X: C-terminal amino acid) motif like the large hepatitis D virus antigen. This modification enables the interaction of the HBV/HDV particle and the virus envelope proteins. Lonafarnib, which prevents this envelopment, has been tested in clinical trials. Targeting the lifecycle of the hepatitis B virus needs to be considered in hepatitis D therapy in order to cure a patient from both coexisting infections. Nucleic acid polymers target the hepatitis B lifecycle in a manner that is not yet understood. Understanding the possible targets of the hepatitis D virus therapy is inevitable for the improvement and development of a sufficient therapy that HDV patients are desperately in need of.

Keywords: Hepcludex; antivirals; farnesyl transferase; hepatitis B; hepatitis D; viral entry mechanisms.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • Cysteine
  • Farnesyltranstransferase
  • Hepatitis B virus / metabolism
  • Hepatitis B* / drug therapy
  • Hepatitis D* / drug therapy
  • Hepatitis D* / metabolism
  • Hepatitis Delta Virus
  • Humans
  • Interferon-alpha / therapeutic use
  • Nucleic Acids* / therapeutic use
  • Polymers / therapeutic use
  • Receptors, Virus
  • Taurocholic Acid
  • Viral Envelope Proteins / metabolism


  • Antiviral Agents
  • Interferon-alpha
  • Nucleic Acids
  • Polymers
  • Receptors, Virus
  • Viral Envelope Proteins
  • Taurocholic Acid
  • Farnesyltranstransferase
  • Cysteine

Grants and funding

This research received no external funding.