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World J Hepatol. Apr 28, 2015; 7(6): 896-902
Published online Apr 28, 2015. doi: 10.4254/wjh.v7.i6.896
Lamivudine resistance in children with chronic hepatitis B
Erhun Kasırga
Erhun Kasırga, Department of Pediatric Gastroenterology, Celal Bayar University, 45030 Manisa, Turkey
Author contributions: Kasırga E designed research, performed research, contributed new reagents or analytic tools, analyzed data and wrote the paper.
Conflict-of-interest: 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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Erhun Kasırga, Professor, Department of Pediatric Gastroenterology, Celal Bayar University, Uncubozköy Mh., Mimarsinan Bulv., No:173, 45030 Manisa, Turkey. hekasirga@hotmail.com
Telephone: +90-236-4444228 Fax: +90-236-2338040
Received: August 26, 2014
Peer-review started: August 27, 2014
First decision: September 16, 2014
Revised: October 31, 2014
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: April 28, 2015
Processing time: 247 Days and 23.5 Hours
Abstract

Currently, although lamivudine (LAM) has a low genetic barrier, only interferon-alpha and LAM are available as a first-line treatment in children with chronic hepatitis B (CHB). LAM is a potent inhibitor of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) polymerase replication by termination of the proviral HBV-DNA chain. LAM has a good safety and tolerability profile in CHB patients with hepatic decompensation. However, the main disadvantages of this HBV reverse transcriptase inhibitor are: (1) pre-existing covalently closed circular DNA cannot be eradicated by LAM, thus relapse after therapy withdrawal is frequent; and (2) although the longer LAM treatment induced the higher seroconversion rate, the risk of viral resistance increased through the selection of YMDD (tyrosine, methionine, aspartate, aspartate) motif. Insufficient suppression of viral replication leads to the emergence of resistant strains that could result in virological breakthrough which is usually followed by biochemical breakthrough. Mutant strains affects additional resistance and cross resistance, leading to drug resistance in a significant number of CHB patients. In this case, efficacy of more powerful anti-viral agents with higher genetic barrier against development of resistance is diminished. Furthermore, strains that are resistant to LAM could bring about vaccine escape mutants, decreasing the efficacy of HBV vaccine. A more potent drug with a high genetic barrier to resistance needs to be approved as the first-line treatment option for CHB in children.

Keywords: Children; Chronic hepatitis B; Lamivudine; Lamivudine-resistant mutants; YMDD mutation

Core tip: In present day, antiviral drugs with higher genotypic barrier to resistance cannot be used for children with chronic hepatitis B since these drugs are not covered by the general health insurance in many countries. Therefore, lamivudine (LAM) which is not used for adults due to its many drawbacks has been used as a first-line of treatment for children out of necessity. Even though long term treatment results with LAM appear to be good, long term treatment increases the possibility of occurrence of resistant strains. These strains which are resistant to LAM could develop cross resistance to other anti-viral agents.