Beyond Pegylated Interferon-Alpha: New Treatments for Hepatitis Delta

AIDS Rev. 2019;21(3):126-134. doi: 10.24875/AIDSRev.19000080.

Abstract

Persistent coinfection with the hepatitis B/D viruses (HDV) represents the most severe form of viral hepatitis. Hepatitis D often leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. The current treatment options are limited as only pegylated interferon-alpha (PEG-IFNa) has efficacy against HDV. However, treatment response is still unsatisfactory with 25-40% HDV RNA suppression after 1-2 years. In addition, late HDV RNA relapses have been described during long-term follow-up. Fortunately, new treatment options for patients with chronic hepatitis delta are now on the horizon. The hepatocyte entry inhibitor bulevirtide (formerly myrcludex B) and the farnesyl transferase inhibitor lonafarnib are currently explored in patients with chronic hepatitis delta in Phase 3 clinical studies. The nucleic acid inhibitor REP-2139-Ca and PEG-IFN-lambda are studied in Phase 2 trials. We here summarize data on the efficacy of these new antiviral drugs and the existing safety data on the treatment of HDV infection.

Keywords: Bulevirtide; Hepatitis B virus/hepatitis D (delta) virus coinfection; Lonafarnib; Myrcludex B; Pegylated interferon-lambda; REP-2139-Ca.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Coinfection / drug therapy
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis D / drug therapy*
  • Hepatitis Delta Virus / drug effects
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / adverse effects
  • Lipopeptides / administration & dosage*
  • Lipopeptides / adverse effects
  • Nucleic Acids / administration & dosage*
  • Nucleic Acids / adverse effects
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects
  • Polymers / administration & dosage*
  • Polymers / adverse effects
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Recurrence
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Lipopeptides
  • Nucleic Acids
  • Piperidines
  • Polymers
  • Pyridines
  • REP 2139
  • myrcludex-B
  • lonafarnib