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World J Hepatol. Jun 27, 2025; 17(6): 107963
Published online Jun 27, 2025. doi: 10.4254/wjh.v17.i6.107963
Hope on the horizon: Emerging therapies for hepatitis D
Zaigham Abbas, Minaam Abbas
Zaigham Abbas, Department of Hepatogastroenterology, Dr. Ziauddin University Hospital Clifton, Karachi 75600, Sindh, Pakistan
Minaam Abbas, Department of Medicine, University of Cambridge, Cambridge CB2 0SP, United Kingdom
Co-first authors: Zaigham Abbas and Minaam Abbas.
Author contributions: Abbas Z and Abbas M contributed equally to this work.
Conflict-of-interest statement: Abbas Z contributed patients to the D-LIVR study. He is the principal investigator from his site for HHoo3, ECLIPSE 1, and 3 studies mentioned in the manuscript.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zaigham Abbas, AGAF, FACG, FACP, FRCP, Head, Professor, Department of Hepatogastroenterology, Dr. Ziauddin University Hospital Clifton, Karachi 75600, Sindh, Pakistan. drzabbas@gmail.com
Received: April 2, 2025
Revised: April 22, 2025
Accepted: June 7, 2025
Published online: June 27, 2025
Processing time: 85 Days and 9 Hours
Abstract

Current treatment options for hepatitis D are limited, with pegylated interferon-alpha (PEG-IFNα) being the only therapy available in the Asia-Pacific region. However, PEG-IFNα has limited efficacy and significant side effects. Pegylated interferon lambda acts on interferon-lambda (Type III) receptors predominantly expressed in hepatocytes. In 2023, bulevirtide was approved in the European Union and Russia for treating chronic hepatitis D. This drug works by binding to and inhibiting the sodium taurocholate co-transporting polypeptide receptor on liver cells, which is the primary entry point for the virus. Recently, several new drugs have entered various stages of development, offering hope for improved hepatitis D virus (HDV) management. Two more viral entry inhibitors are HH003 and tobevibart. Other agents include nucleic acid polymers (REP 2139-Mg), prenylation inhibitors (lonafarnib), and RNA interference-based therapies (elebsiran). Emerging trials are now considering combination therapies, such as SOLSTICE, a Phase 2 clinical trial evaluating tobevibart alone or combined with elebsiran. The combination dosed monthly achieved > 50% virologic and biochemical response at 24 weeks of therapy. The efficacy and safety of these drugs will further be evaluated in ECLIPSE 1, 2, and 3 trials. With these new treatments on the horizon, the prospects for improved HDV patient outcomes are promising.

Keywords: Hepatitis D; Hepatitis B; Treatment; Pegylated interferon; Bulevirtide; Nucleic acid polymers; Lonafarnib; Tobevibart; Elebsiran

Core Tip: New therapeutic options for hepatitis D are emerging, offering hope for improved treatment outcomes. Pegylated interferon-alpha is currently the primary treatment for hepatitis D, but it has limitations, including significant adverse effects and low response rates. Several novel therapies are being developed. Bulevirtide, HH003, and tobevibart are entry inhibitors. Other drugs include pegylated interferon-lambda, a type III interferon; lonafarnib, a prenylation inhibitor that prevents viral replication with synergistic effects when combined with pegylated interferon-alpha; REP 2139, a nucleic acid polymer that inhibits virus entry and replication; and small interfering RNAs, including elebsiran that interfere with translation of hepatitis B virus RNA.