Bianca C, Sidhartha E, Tiribelli C, El-Khobar KE, Sukowati CHC. Role of hepatitis B virus in development of hepatocellular carcinoma: Focus on covalently closed circular DNA . World J Hepatol 2022; 14(5): 866-884 [PMID: 35721287 DOI: 10.4254/wjh.v14.i5.866]
Corresponding Author of This Article
Caecilia H C Sukowati, BSc, PhD, Senior Researcher, Centro Studi Fegato, Fondazione Italiana Fegato ONLUS, AREA Science Park, campus Basovizza, SS14 km 163.5, Trieste 34149, Italy. caecilia.sukowati@fegato.it
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
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/
World J Hepatol. May 27, 2022; 14(5): 866-884 Published online May 27, 2022. doi: 10.4254/wjh.v14.i5.866
Role of hepatitis B virus in development of hepatocellular carcinoma: Focus on covalently closed circular DNA
Claryssa Bianca, Elizabeth Sidhartha, Claudio Tiribelli, Korri Elvanita El-Khobar, Caecilia H C Sukowati
Claryssa Bianca, Elizabeth Sidhartha, Department of Biomedicine, Indonesia International Institute for Life Sciences, Jakarta 13210, Indonesia
Claudio Tiribelli, Caecilia H C Sukowati, Centro Studi Fegato, Fondazione Italiana Fegato ONLUS, Trieste 34149, Italy
Korri Elvanita El-Khobar, Caecilia H C Sukowati, Eijkman Center for Molecular Biology, National Research and Innovation Agency (BRIN), Jakarta 10340, Indonesia
Author contributions: El-Khobar KE and Sukowati CHC conceived the idea; Bianca C, Sidhartha E, Tiribelli C, El-Khobar KE, and Sukowati CHC wrote the manuscript; all authors read and approved the manuscript.
Supported byInternational Cooperation 2021 with Indonesia from the Regione of Friuli Venezia Giulia (Prot. 0015911/P) to the FIF.
Conflict-of-interest statement: All authors declare that there are no conflicts of interest to disclose.
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: Caecilia H C Sukowati, BSc, PhD, Senior Researcher, Centro Studi Fegato, Fondazione Italiana Fegato ONLUS, AREA Science Park, campus Basovizza, SS14 km 163.5, Trieste 34149, Italy. caecilia.sukowati@fegato.it
Received: November 30, 2021 Peer-review started: November 30, 2021 First decision: December 26, 2021 Revised: January 31, 2022 Accepted: April 25, 2022 Article in press: April 25, 2022 Published online: May 27, 2022
Abstract
Chronic infection with hepatitis B virus (HBV) remains a major global health problem, especially in developing countries. It may lead to prolonged liver damage, fibrosis, cirrhosis, and hepatocellular carcinoma. Persistent chronic HBV infection is related to host immune response and the stability of the covalently closed circular DNA (cccDNA) in human hepatocytes. In addition to being essential for viral transcription and replication, cccDNA is also suspected to play a role in persistent HBV infections or hepatitis relapses since cccDNA is very stable in non-dividing human hepatocytes. Understanding the pathogenicity and oncogenicity of HBV components would be essential in the development of new diagnostic tools and treatment strategies. This review summarizes the role and molecular mechanisms of HBV cccDNA in hepatocyte transformation and hepatocarcinogenesis and current efforts to its detection and targeting.
Core Tip: The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) in human hepatocytes serves as the template for viral replication machinery. HBV cccDNA is also related to host immune response and persistent HBV infection leading to the development of hepatocellular carcinoma. This review summarizes current knowledge on cccDNA in hepatocarcinogenesis and comprehensive efforts to its detection and targeting.
