Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 18, 2015; 7(5): 777-786
Published online Apr 18, 2015. doi: 10.4254/wjh.v7.i5.777
Hepatitis D and hepatocellular carcinoma
Zaigham Abbas, Minaam Abbas, Sarim Abbas, Lubna Shazi
Zaigham Abbas, Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
Minaam Abbas, University of Cambridge, Cambridge CB2 1TB, United Kingdom
Sarim Abbas, Lubna Shazi, LiverStomach Clinic, Akber Centre, Karachi 75500, Pakistan
Author contributions: Abbas Z designed the review’s objectives; Abbas Z and Abbas M searched the literature for the latest developments in the field related to epidemiology and cell pathways; Abbas S designed the figure; Shazi L summarized the studies for the table; all authors were involved in reviewing the literature, writing and editing the manuscript.
Conflict-of-interest: 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 74200, Pakistan. drzabbas@gmail.com
Telephone: +92-21-32728998 Fax: +92-21-32728998
Received: August 19, 2014
Peer-review started: August 19, 2014
First decision: September 16, 2014
Revised: December 21, 2014
Accepted: January 15, 2015
Article in press: January 19, 2015
Published online: April 18, 2015
Processing time: 243 Days and 15.5 Hours
Abstract

Hepatitis D virus (HDV) is a defective circular shape single stranded HDV RNA virus with two types of viral proteins, small and large hepatitis D antigens, surrounded by hepatitis B surface antigen. Superinfection with HDV in chronic hepatitis B is associated with a more threatening form of liver disease leading to rapid progression to cirrhosis. In spite of some controversy in the epidemiological studies, HDV infection does increase the risk of hepatocellular carcinoma (HCC) compared to hepatitis B virus (HBV) monoinfection. Hepatic decompensation, rather than development of HCC, is the first usual clinical endpoint during the course of HDV infection. Oxidative stress as a result of severe necroinflammation may progress to HCC. The large hepatitis D antigen is a regulator of various cellular functions and an activator of signal transducer and activator of transcription (STAT)3 and the nuclear factor kappa B pathway. Another proposed epigenetic mechanism by which HCC may form is the aberrant silencing of tumor suppressor genes by DNA Methyltransferases. HDV antigens have also been associated with increased histone H3 acetylation of the clusterin promoter. This enhances the expression of clusterin in infected cells, increasing cell survival potential. Any contribution of HBV DNA integration with chromosomes of infected hepatocytes is not clear at this stage. The targeted inhibition of STAT3 and cyclophilin, and augmentation of peroxisome proliferator-activated receptor γ have a potential therapeutic role in HCC.

Keywords: Hepatitis D; Hepatocellular carcinoma; Necroinflammation; Epigenetic processes; Cirrhosis; Oxidative stress

Core tip: Role of hepatitis D virus (HDV) in the oncogenesis of hepatocellular carcinoma (HCC) has not been thoroughly investigated. Many epidemiological studies favour the increased risk of HCC with HDV superinfection. Oxidative stress as a result of severe necroinflammation may trigger the development of HCC. Epigenetic mechanisms like DNA methylation and histone modification may also be operating.