摘要
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 virusdeoxyribonucleic 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 LAMtreatment 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.
Currently, although lamivudine （LAM） has a low geneticbarrier, only interferon-alpha and LAM are available asa first-line treatment in children with chronic hepatitisB （CHB）. LAM is a potent inhibitor of hepatitis B virusdeoxyribonucleicacid （HBV-DNA） polymerase replicationby termination of the proviral HBV-DNA chain. LAM hasa good safety and tolerability profile in CHB patientswith hepatic decompensation. However, the maindisadvantages of this HBV reverse transcriptase inhibitorare： （1） pre-existing covalently closed circular DNAcannot be eradicated by LAM, thus relapse after therapywithdrawal is frequent; and （2） although the longer LAMtreatment induced the higher seroconversion rate, therisk of viral resistance increased through the selectionof YMDD （tyrosine, methionine, aspartate, aspartate）motif. Insufficient suppression of viral replication leadsto the emergence of resistant strains that could resultin virological breakthrough which is usually followedby biochemical breakthrough. Mutant strains affectsadditional resistance and cross resistance, leading todrug resistance in a significant number of CHB patients.In this case, efficacy of more powerful anti-viral agentswith higher genetic barrier against development ofresistance is diminished. Furthermore, strains that areresistant to LAM could bring about vaccine escapemutants, decreasing the efficacy of HBV vaccine. A morepotent drug with a high genetic barrier to resistanceneeds to be approved as the first-line treatment optionfor CHB in children.
