Lamivudine resistance in children with chronic hepatitis B.
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.
Erhun Kasırga, Department of Pediatric Gastroenterology, Celal Bayar University, 45030 Manisa, Turkey.
Erhun
E
Kasırga
Children; Chronic hepatitis B; Lamivudine; Lamivudine-resistant mutants; YMDD mutation