Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 8, 2015; 7(13): 1742-1754
Published online Jul 8, 2015. doi: 10.4254/wjh.v7.i13.1742
Nucleos(t)ide analogs in the prevention of hepatitis B virus related hepatocellular carcinoma
Bulent Baran
Bulent Baran, Department of Gastroenterology, Koç University Hospital, Zeytinburnu, 34010 Istanbul, Turkey
Author contributions: Baran B performed literature search and wrote the whole manuscript.
Conflict-of-interest statement: None.
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:
Correspondence to: Bulent Baran, MD, FEBG, Department of Gastroenterology, Koç University Hospital, Davutpasa St., Zeytinburnu, 34010 Istanbul, Turkey.
Telephone: +90-850-2508250 Fax: +90-212-3112277
Received: January 29, 2015
Peer-review started: February 2, 2015
First decision: April 10, 2015
Revised: May 6, 2015
Accepted: June 18, 2015
Article in press: June 19, 2015
Published online: July 8, 2015

Hepatocellular carcinoma (HCC) is among the most common cancer types and causes of cancer related mortality worldwide. Almost 50% of all HCC cases globally are attributable to chronic hepatitis B virus (HBV) infection. The incidence rates of HCC in untreated Asian subjects with HBV infection was estimated to be 0.2% in inactive carriers, 0.6% for those with chronic hepatitis without cirrhosis, and 3.7% for those with compensated cirrhosis. In Western populations, HCC incidences are reported to be 0.02% in inactive carriers, 0.3% in subjects with chronic hepatitis without cirrhosis, and 2.2% in subjects with compensated cirrhosis. Despite effective antiviral treatment options which are able to transform chronic hepatitis into an inactive carrier state, the risk of HCC cannot be fully ruled out to exclude those patients from surveillance. Newer nucleos(t)ide analogues (NAs) as entecavir and tenofovir are very potent in terms of sustained virological suppression which leads to improved liver histology. However, they do not have any influence on the cccDNA or integrated DNA of HBV in the liver. Nonetheless, viral replication is the only modifiable component among the established risk factors for HBV-related HCC with the current treatment options. In this review, it was aimed to summarize cumulative evidence behind the concept of prevention of HBV related HCC by NAs, and to discuss remaining obstacles to eliminate the risk of HCC.

Keywords: Hepatitis B virus, Hepatocellular carcinoma, Prevention, Nucleos(t)ide analogues, Risk factors

Core tip: After the introduction of potent nucleos(t)ide analogues with high genetic barrier to resistance, maintaining long-term virological suppression is achievable in almost all patients with chronic hepatitis B. The currently recommended first-line antiviral drugs, entecavir and tenofovir, can significantly reduce hepatocellular carcinoma (HCC) incidence, but the observed risk under efficient therapy is not zero in the long-term. There are established risk factors including age, gender, family history, low platelet levels, presence of cirrhosis or severity of liver disease, which should be incorporated into the clinical decision making to differentiate those patients under risk of developing HCC.