AIM:To identify hepatitis B virus polymerase gene mutations during antiviral therapy using lamivudineadefovir sequential monotherapy followed by lamivudine-adefovir combination therapy.METHODS:The patient cohort inclu...AIM:To identify hepatitis B virus polymerase gene mutations during antiviral therapy using lamivudineadefovir sequential monotherapy followed by lamivudine-adefovir combination therapy.METHODS:The patient cohort included four adult chronic hepatitis B patients who had undergone sequential monotherapy,first with lamivudine(LMV) and then,after developing viral breakthrough,with adefovir(ADV) therapy.All of the patients had non-response or viral breakthrough after LMV-ADV sequential monotherapy,which resulted in the switching of their antiviral regimen to LMV-ADV combination therapy.Eleven serum samples from the four patients who showed non-response to rescue LMV-ADV combination therapy were collected sequentially at a time before the antiviral treatment and then during the LMV monotherapy,ADV monotherapy,and LMV-ADV combination therapy.For the genotypic analysis,the whole 1310-bp polymerase gene region was amplified,cloned and sequenced.RESULTS:All patients had been previously treated with 100 mg of LMV once daily for a 15-to 26-mo period.The emergence of resistance mutations to LMV,such as rtM204V/I and/or rtL180M,were found in all patients.Their antiviral regimens were switched to ADV monotherapy as the second line treatment.All patients had viral breakthrough or non-response after the LMV-ADV sequential monotherapy.ADV-resistant mutations were detected after 13 to 19 mo of LMV-ADV sequential monotherapy.The rtA181V/T mutations were predominantly identified during the ADV treatment in the LMV-resistant patients.Twenty-seven of 38 clones were combined with an amino acid change at rt181;three clones had mutations in rt236 and one clone had a combined mutation.The rtA181V/T mutations were not suppressed by the LMV-ADV combination therapy.Thirty-nine of 64 clones showed an rtA181V/T mutation and six clones showed combined mutations in rt181 and rt236.Mutations in rt204 re-emerged during the combination treatment.The rt181 and rt204 mutations did not co-exist in one clone.CONCLUSION:Add-on lamivudine therapy with adefovir for adefovir resistance may not suppress the pre-existing adefovir-resistant mutation that develops during lamivudine-adefovir sequential monotherapy.展开更多
A hepatitis B virus （HBV） model with standard incidence and the uninfected cells growing logistically is investigated. By analyzing the corresponding characteristic equations, the local stability of the infection-fr...A hepatitis B virus （HBV） model with standard incidence and the uninfected cells growing logistically is investigated. By analyzing the corresponding characteristic equations, the local stability of the infection-free and infection equilibria is discussed, respectively. Further, the existence of an orbitally asymptotically stable periodic orbit is also studied. By means of the theory of competitive systems and compound matrices, sufficient conditions are derived for the global stability of the infection-free and infection equilibria, respectively. At last, numerical simulations are carried out to illustrate the main results.展开更多
基金Supported by A grant from the South Korea Heathcare Technology R and D Project,Ministry for Health,Welfare and Family Affairs,South Korea,No.A084826
文摘AIM:To identify hepatitis B virus polymerase gene mutations during antiviral therapy using lamivudineadefovir sequential monotherapy followed by lamivudine-adefovir combination therapy.METHODS:The patient cohort included four adult chronic hepatitis B patients who had undergone sequential monotherapy,first with lamivudine(LMV) and then,after developing viral breakthrough,with adefovir(ADV) therapy.All of the patients had non-response or viral breakthrough after LMV-ADV sequential monotherapy,which resulted in the switching of their antiviral regimen to LMV-ADV combination therapy.Eleven serum samples from the four patients who showed non-response to rescue LMV-ADV combination therapy were collected sequentially at a time before the antiviral treatment and then during the LMV monotherapy,ADV monotherapy,and LMV-ADV combination therapy.For the genotypic analysis,the whole 1310-bp polymerase gene region was amplified,cloned and sequenced.RESULTS:All patients had been previously treated with 100 mg of LMV once daily for a 15-to 26-mo period.The emergence of resistance mutations to LMV,such as rtM204V/I and/or rtL180M,were found in all patients.Their antiviral regimens were switched to ADV monotherapy as the second line treatment.All patients had viral breakthrough or non-response after the LMV-ADV sequential monotherapy.ADV-resistant mutations were detected after 13 to 19 mo of LMV-ADV sequential monotherapy.The rtA181V/T mutations were predominantly identified during the ADV treatment in the LMV-resistant patients.Twenty-seven of 38 clones were combined with an amino acid change at rt181;three clones had mutations in rt236 and one clone had a combined mutation.The rtA181V/T mutations were not suppressed by the LMV-ADV combination therapy.Thirty-nine of 64 clones showed an rtA181V/T mutation and six clones showed combined mutations in rt181 and rt236.Mutations in rt204 re-emerged during the combination treatment.The rt181 and rt204 mutations did not co-exist in one clone.CONCLUSION:Add-on lamivudine therapy with adefovir for adefovir resistance may not suppress the pre-existing adefovir-resistant mutation that develops during lamivudine-adefovir sequential monotherapy.
文摘A hepatitis B virus （HBV） model with standard incidence and the uninfected cells growing logistically is investigated. By analyzing the corresponding characteristic equations, the local stability of the infection-free and infection equilibria is discussed, respectively. Further, the existence of an orbitally asymptotically stable periodic orbit is also studied. By means of the theory of competitive systems and compound matrices, sufficient conditions are derived for the global stability of the infection-free and infection equilibria, respectively. At last, numerical simulations are carried out to illustrate the main results.
