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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 by International 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:
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.
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
Core Tip

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.