Minireviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2019; 11(1): 65-73
Published online Jan 27, 2019. doi: 10.4254/wjh.v11.i1.65
Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure
Brianna J Shinn, Aaron Martin, Robert M Coben, Mitchell I Conn, Jorge Prieto, Howard Kroop, Anthony J DiMarino, Hie-Won Hann
Brianna J Shinn, Aaron Martin, Robert M Coben, Mitchell I Conn, Jorge Prieto, Howard Kroop, Anthony J DiMarino, Hie-Won Hann, Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States
Author contributions: Hann HW contributed the conception and design of the manuscript, Shinn BJ wrote the paper; Martin A reviewed and also assisted in writing of the paper; Coben RM, Conn MI, Prieto J, Kroop H and DiMarino AJ were all involved with the medical care of the patients mentioned in this manuscript; all contributed in finalizing the paper.
Conflict-of-interest statement: Hann HW receives Research grant from Gilead Sciences, Assembly Biosciences and TriHealth. Shinn BJ, Martin A, Coben RM, Conn MI, Prieto J, Kroop H and DiMarino AJ have no conflict 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/
Corresponding author: Hie-Won Hann, MD, FAASLD, Professor, Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, 1025 Walnut Street, Philadelphia, PA 19107, United States. hie-won.hann@jefferson.edu
Telephone: +1-215-9555806 Fax: +1-215-9550770
Received: September 27, 2018
Peer-review started: September 27, 2018
First decision: October 16, 2018
Revised: November 14, 2018
Accepted: December 31, 2018
Article in press: January 1, 2019
Published online: January 27, 2019
Abstract

Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA (cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure (loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.

Keywords: Hepatitis B, Hepatocellular carcinoma, Antiviral therapy, Persistent Risk for hepatocellular carcinoma, Tumor ablation

Core tip: Despite the advances in the management of hepatitis B virus (HBV) infection and HBV-associated hepatocellular carcinoma (HCC), the risk for new, subsequent new and recurrent HCC persists even after over a decade of antiviral therapy and initial tumor ablation. This is due to the inability of the current antiviral therapy to eliminate the covalently closed circular DNA from the hepatocyte nucleus. There is a great need for an HBV cure drug.