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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2016; 22(4): 1497-1512
Published online Jan 28, 2016. doi: 10.3748/wjg.v22.i4.1497
Significance of hepatitis virus infection in the oncogenic initiation of hepatocellular carcinoma
Caecilia HC Sukowati, Korri E El-Khobar, Susan I Ie, Beatrice Anfuso, David H Muljono, Claudio Tiribelli
Caecilia HC Sukowati, Beatrice Anfuso, Claudio Tiribelli, Fondazione Italiana Fegato ONLUS, AREA Science Park Basovizza, 34149 Trieste, Italy
Caecilia HC Sukowati, Claudio Tiribelli, Department of Medicine, Surgery, and Health Sciences, University of Trieste, Teaching Hospital Cattinara, 34149 Trieste, Italy
Korri E El-Khobar, Susan I Ie, David H Muljono, Laboratory of Hepatitis and Emerging Disease, Eijkman Institute for Molecular Biology, Jakarta 10430, Indonesia
Korri E El-Khobar, Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, NSW 2145, Australia
Author contributions: Sukowati CHC designed the review scheme and wrote the manuscript; El-Khobar KE, Ie SI and Anfuso B wrote the manuscript; Muljono DH and Tiribelli C provided idea and feedback of the manuscript; all authors read and approved the manuscript.
Conflict-of-interest statement: All authors have no conflicts of interest.
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: Caecilia HC Sukowati, PhD, Fondazione Italiana Fegato ONLUS, AREA Science Park Basovizza, SS14 km 163.5, 34149 Trieste, Italy. caecilia.sukowati@csf.units.it
Telephone: +39-40-3757926 Fax: +39-40-3757832
Received: May 28, 2015
Peer-review started: June 1, 2015
First decision: July 14, 2015
Revised: August 6, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: January 28, 2016
Abstract

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, and DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.

Keywords: Hepatocellular carcinoma, Hepatitis B virus, Hepatitis C virus, Oncogenicity, Viral pathogenicity

Core tip: According to the most recent data released by the International Agency for Research on Cancer-World Health Organization, liver cancer is the second most common cause of cancer mortality worldwide. Hepatocellular carcinoma (HCC) accounts for around 90% of liver cancer cases and it is variably distributed according to its main risk factors. The hepatotropic viral [hepatitis B virus (HBV) and hepatitis C virus (HCV)] infection can cause a disarrangement in cellular pathways through an indirect and/or direct mechanism in liver injury. This review summarize available data in literature regarding the oncogenic properties of HBV and HCV in the initiation of HCC, including their role in the activation of hepatic stem cells.