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Sukowati et al. Hepatoma Res 2019;5:2 Hepatoma Research
DOI: 10.20517/2394-5079.2018.106

Review Open Access

Oncogenicity of viral hepatitis B and C in the
initiation of hepatic cancer stem cells

1,3
1,2
Caecilia H. C. Sukowati , Peter A. C. Reyes , Gianluca Tell , Claudio Tiribelli 1
1,2
1 Fondazione Italiana Fegato, Trieste 34149, Italy.
2 Dipartimento di Area Medica, University of Udine, Udine 33100, Italy.
3 Hepatology Society of the Philippines, Loyola Heights Quezon City 1108, Philippines.
Correspondence to: Dr. Caecilia H. C. Sukowati, Fondazione Italiana Fegato, AREA Science Park Basovizza, Trieste 34149, Italy.
E-mail: caecilia.sukowati@fegato.it

How to cite this article: Sukowati CHC, Reyes PAC, Tell G, Tiribelli C. Oncogenicity of viral hepatitis B and C in the initiation of hepatic
cancer stem cells. Hepatoma Res 2019;5:2. http://dx.doi.org/10.20517/2394-5079.2018.106

Received: 15 Oct 2018 First Decision: 2 Nov 2018 Revised: 22 Nov 2018 Accepted: 6 Dec 2018 Published: 16 Jan 2019
Science Editor: Lei Chen Copy Editor: Cui Yu Production Editor: Huan-Liang Wu

Abstract
Chronic infection of hepatitis B virus (HBV) or/and hepatitis C virus (HCV) is one of major risk factors in the
development of the hepatocellular carcinoma. Recent studies had shown the capacity of viral proteins in inducing
the presence of the population of so-called the cancer stem cells (CSC). The integration of HBV S and X gene in
the host genome indicates its direct oncogenicity. In addition, the presence HBV and HCV proteins were shown to
modulate intracellular molecular pathways and epigenetic modification. This review summarizes current literature
regarding direct oncogenic properties of HBV and HCV in the initiation of CSC both in in vitro and in vivo studies.

Keywords: Cancer stem cells, hepatocellular carcinoma, hepatitis B virus, hepatitis C virus

INTRODUCTION
Chronic infection of viral hepatitis B or C is a major risk factor for the development of hepatocellular
carcinoma (HCC). In fact, global distribution of HCC is associated with the prevalence of hepatitis viruses:
hepatitis B virus (HBV) or hepatitis C virus (HCV). The infection of endemic HBV is the major cause
of HCC in eastern Asia and sub-Saharan Africa for around 70%, while in Europe and North American
countries, the infection of HCV ranges from 50% to 70% of all cases [1-3] . In addition, due to different
oncogenic mechanisms of viruses, as well as various genetic host background and long-term development of
the disease, viral-related HCCs show high heterogeneity.

Hepatocarcinogenesis is multifactorial, consisting of various steps in a long-term course. At its initiation,
disturbance in the molecular and cellular pathways might result in the malignant transformation from

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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