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World J Gastroenterol. Jun 28, 2021; 27(24): 3530-3542
Published online Jun 28, 2021. doi: 10.3748/wjg.v27.i24.3530
Hepatitis delta virus: From infection to new therapeutic strategies
Grazia A Niro, Arianna Ferro, Francesca Cicerchia, Isabella Brascugli, Marilena Durazzo
Grazia A Niro, Department of Gastroenterology, IRCCS Casa Sollievo della Sofferenza Hospital Foundation, San Giovanni Rotondo 71013, Italy
Arianna Ferro, Francesca Cicerchia, Isabella Brascugli, Marilena Durazzo, Department of Medical Sciences, University of Turin, Turin 10126, Italy
Author contributions: Niro GA and Durazzo M designed the review and critically revised the work; Ferro A, Cicerchia F and Brascugli I performed the research and wrote the paper; All authors have read and approve the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marilena Durazzo, MD, Associate Professor, Department of Medical Sciences, University of Turin, C So AM Dogliotti 14, Turin 10126, Italy. marilena.durazzo@unito.it
Received: February 7, 2021
Peer-review started: February 7, 2021
First decision: April 5, 2021
Revised: April 7, 2021
Accepted: May 27, 2021
Article in press: May 27, 2021
Published online: June 28, 2021
Abstract

The hepatitis delta virus (HDV) is a small RNA virus that encodes a single protein and which requires the hepatitis B virus (HBV)-encoded hepatitis B surface antigen (HBsAg) for its assembly and transmission. HBV/HDV co-infections exist worldwide and show a higher prevalence among selected groups of HBV-infected populations, specifically intravenous drug users, practitioners of high-risk sexual behaviours, and patients with cirrhosis and hepatocellular carcinoma. The chronic form of HDV-related hepatitis is usually severe and rapidly progressive. Patterns of the viral infection itself, including the status of co-infection or super-infection, virus genotypes (both for HBV and HDV), and persistence of the virus’ replication, influence the outcome of the accompanying and manifested liver disease. Unfortunately, disease severity is burdened by the lack of an effective cure for either virus type. For decades, the main treatment option has been interferon, administered as mono-therapy or in combination with nucleos(t)ide analogues. While its efficacy has been reported for different doses, durations and courses, only a minority of patients achieve a sustained response, which is the foundation of eventual improvement in related liver fibrosis. The need for an efficient therapeutic alternative remains. Research efforts towards this end have led to new treatment options that target specific steps in the HDV life cycle; the most promising among these are myrcludex B, which inhibits virus entry into hepatocytes, lonafarnib, which inhibits farnesylation of the viral-encoded L-HDAg large hepatitis D antigen, and REP-2139, which interferes with HBsAg release and assembly.

Keywords: Hepatitis delta virus, Hepatitis B virus, Myrcludex, Lonafarnib, REP 2139

Core Tip: The hepatitis delta virus (HDV) is a small defective virus, of interest to scientists for its replicative reliance on and ability to inhibit the common hepatitis B virus (HBV). HDV infection occurs worldwide but shows some geographic variation and its prevalence is generally underestimated. HDV/HBV co-infection causes severe liver disease and the persistence of viral replication is associated with poor prognosis, although interferon is effective in around a quarter of patients. Improved understanding of the HDV life cycle has led to identification of specific antiviral targets and new drugs, including inhibitors of the sodium tauro-cholate cotransporting polypeptide receptor and farnesyltransferase.