Current and future management of chronic hepatitis D

Patrizia Farci, Grazia Anna Niro

Research output: Contribution to journalArticle

Abstract

Hepatitis D virus (HDV) is a defective RNA virus that requires the hepatitis B surface antigen (HBsAg) of the hepatitis B virus (HBV) for its assembly, release, and transmission. HDV is highly pathogenic, causing the least common, but most severe, form of chronic viral hepatitis at all ages. Although significant advances have been made in the treatment of chronic viral hepatitis, targeting HDV remains a major challenge because of the unconventional nature of this virus and the severity of its disease. The virus contains a ribonucleoprotein complex formed by the RNA genome with a single structural protein, delta antigen (HDAg), which exists in 2 forms (small and large HDAg) and is coated by HBsAg. Farnesylation of the large HDAg is essential for anchoring the ribonucleoprotein to HBsAg for the assembly of virion particles. HDV enters into hepatocytes by using the HBV receptor, the sodium taurocholate cotransporting polypeptide (NTCP). Unlike other RNA viruses, HDV does not encode its own polymerase but exploits the host RNA polymerase II for replication. Thus, in contrast to HBV and hepatitis C virus, which possess virus-specific enzymes that can be targeted by specific inhibitors, the lack of a virus-specific polymerase makes HDV a particularly challenging therapeutic target. Treatment of hepatitis D remains unsatisfactory, and interferon-a has been the only approved drug over the past 30 years. This article examines the unconventional nature of HDV, the current management of chronic hepatitis D, and how new insights from the HDV life cycle have led to the development of 3 novel classes of drugs (NTCP receptor inhibitors, farnesyltransferase inhibitors, and nucleic acid polymers) that are currently under clinical evaluation.

Original languageEnglish
Pages (from-to)342-351
Number of pages10
JournalGastroenterology and Hepatology
Volume14
Issue number6
Publication statusPublished - Jun 1 2018

Fingerprint

Chronic Hepatitis D
Hepatitis Delta Virus
Hepatitis delta Antigens
Hepatitis B Surface Antigens
Hepatitis B virus
Viruses
Ribonucleoproteins
RNA Viruses
Chronic Hepatitis
Hepatitis D
Farnesyltranstransferase
Prenylation
Defective Viruses
Virus Receptors
Drug Receptors
Virus Assembly
RNA Polymerase II
Life Cycle Stages
Hepacivirus
Virion

Keywords

  • Chronic hepatitis D
  • Hepatitis D virus
  • Lonafarnib
  • Myrcludex B
  • Pegylated interferon
  • REP 2139
  • Standard interferon
  • Treatment

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Current and future management of chronic hepatitis D. / Farci, Patrizia; Niro, Grazia Anna.

In: Gastroenterology and Hepatology, Vol. 14, No. 6, 01.06.2018, p. 342-351.

Research output: Contribution to journalArticle

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