Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2015; 21(32): 9461-9465
Published online Aug 28, 2015. doi: 10.3748/wjg.v21.i32.9461
Management of hepatitis delta: Need for novel therapeutic options
Zaigham Abbas, Minaam Abbas
Zaigham Abbas, Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
Minaam Abbas, University of Cambridge, CB2 1TP Cambridge, United Kingdom
Author contributions: Abbas Z designed the review’s objectives; both authors were involved in reviewing the literature, writing and editing the manuscript.
Conflict-of-interest statement: Authors do not have any conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Dr. Zaigham Abbas, FCPS, FRCP, Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi 75500, Pakistan. drzabbas@gmail.com
Telephone: +92-21-32728998 Fax: +92-21-32728998
Received: December 26, 2014
Peer-review started: December 26, 2014
First decision: February 10, 2015
Revised: February 23, 2015
Accepted: June 9, 2015
Article in press: June 10, 2015
Published online: August 28, 2015
Processing time: 245 Days and 15 Hours
Abstract

Hepatitis D virus (HDV) is the smallest single stranded RNA virus infecting humans. The hepatitis B surface antigen envelope protein protects the HDV nucleocapsid antigen and provides a means for the virus to enter and exit the hepatocyte. Hepatitis B and D viruses exploit the human sodium taurocholate co-transporting polypeptide (NTCP), a receptor, for their entry into hepatocytes. Prenylation of the large delta antigen is a critical determinant of HDV particle assembly. Treatment with pegylated interferon results in sustained virological response six months post-treatment in one fourth of the patients. Nucleos(t)ide analogs (NAs) have been widely tested in hepatitis delta, but they appear to be ineffective. Combination treatment of NAs with interferon also proved to be disappointing so there is a need for novel therapeutic options. The receptor function of NTCP is blocked by Myrcludex B, a synthetic N-acylated preS1 lipopeptide that competes with infectious virions for receptor binding. There are already some approved drugs available, including irbesartan, ezetimibe, and ritonavir and cyclosporin A, with documented inhibitory effects on NTCP’s metabolic function. These drugs may have a role in HDV treatment. Interference with host-mediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation may become an important tool to control HDV infection and prevent replication. Lonafarnib, a prenylation inhibitor significantly reduces virus levels in hepatitis delta patients. Antisense oligodeoxynucleotides which are complementary to genomic HDV ribozyme self-cleavage site and stem I regions can inhibit genomic HDV ribozyme activity.

Keywords: Hepatitis D virus; Hepatitis delta; Interferon; Lonafarnib; Prenylation inhibitors; Myrcludex

Core tip: The human sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a functional, preS1-specific receptor for hepatitis B and D virus entry. New antiviral drugs will target this receptor to control hepatitis delta infection. There are already a few approved drugs available in the market with inhibitory effects on NTCP. Interference with host-mediated post-translational changes of proteins that are crucial to the Hepatitis D virus (HDV) life cycle, such as prenylation may become an important tool to prevent HDV replication. These developments are important since pegylated interferon maintains a sustained virological response in just a quarter of all patients.