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World J Hepatol. Feb 18, 2017; 9(5): 227-241
Published online Feb 18, 2017. doi: 10.4254/wjh.v9.i5.227
Adverse effects of oral antiviral therapy in chronic hepatitis B
Bircan Kayaaslan, Rahmet Guner
Bircan Kayaaslan, Rahmet Guner, Department of Infectious Disease and Clinical Microbiology, Yildirim Beyazit University Faculty of Medicine, Ataturk Education and Research Hospital, 06800 Ankara, Turkey
Author contributions: Both authors contributed equally to this paper with conception and design of the study, literature review and analysis, and drafting, critical revision, editing and approval of the final version.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
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: Bircan Kayaaslan, MD, Department of Infectious Disease and Clinical Microbiology, Yildirim Beyazit University Faculty of Medicine, Ataturk Education and Research Hospital, Bilkent Street no: 1, 06800 Ankara, Turkey.
Telephone: +90-505-8267777
Received: April 28, 2016
Peer-review started: May 2, 2016
First decision: November 18, 2016
Revised: November 29, 2016
Accepted: December 7, 2016
Article in press: December 9, 2016
Published online: February 18, 2017

Oral nucleoside/nucleotide analogues (NAs) are currently the backbone of chronic hepatitis B (CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects (i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a “Black Box” warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus (HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment.

Keywords: Nucleoside/nucleotide analogues, Adverse events, Lamivudine, Chronic hepatitis B, Side effects, Safety, Telbivudine, Hepatitis B infection, Adefovir, Entecavir, Adverse effects, Tenofovir, Hepatitis B virus

Core tip: Extrahepatic effects of nucleotide analogues (i.e., myopathy, nephropathy, bone disorders) are more commonly indicated in current reports. Some of these adverse events can be attributed to their effect of causing mitochondrial dysfunction. These adverse events are named as “class effects” and mostly associated with lamivudine and telbivudine treatment. Adefovir is a well-known nephrotoxic agent. Nephrotoxic and bone density loss effects of tenofovir in patients with chronic hepatitis B (CHB) are not as clear as in those with human immunodeficiency virus infection. Serum creatinine, phosphorus and creatine kinase levels should be monitored. Safety profile is a major issue that should not be ignored in the treatment of CHB.