Rescue therapy for lamivudine-resistant chronic hepatitis B: Comparison between entecavir 1.0 mg monotherapy, adefovir monotherapy and adefovir add-on lamivudine combination therapy
Rescue therapy for lamivudine-resistant chronic hepatitis B: Comparison between entecavir 1.0 mg monotherapy, adefovir monotherapy and adefovir add-on lamivudine combination therapy
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DOI：
10.1111/j.1440-1746.2010.06381.x
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发表时间：
2010-08-01
影响因子：
4.1
通讯作者：
Kim, Byung Ik
中科院分区：
文献类型：
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作者：
Kim, Hong Joo;Park, Jung Ho;Kim, Byung Ik
背景与目的：阿德福韦酯（ADV）和恩替卡韦（ETV）挽救治疗拉米夫定（LAM）耐药的慢性B型肝炎（CH B）的疗效比较尚未见报道。比较ETV 1.0 mg单药治疗、ADV单药治疗和ADV加LAM联合治疗难治性LAM患者的累积疗效和耐药性（1.0 mg，每日一次）;第2组（n = 44），LAM转换为ADV第3组（n = 36），在LAM基础上加用ADV（10毫克一天一次）。经过6个月的补救治疗，在接受ETV单药治疗、ADV单药治疗和ADV添加治疗的患者中，丙氨酸氨基转移酶恢复正常的比例分别为75.0%、65.9%和74.3%，分别与ETV组相比，ADV添加组在6个月时HBV-DNA下降的log（10）显著更高。ETV单药治疗、ADV单药治疗和ADV加用治疗后6个月HBV-DNA聚合酶链反应阴性率（< 300拷贝/mL）分别为33.3%、27.3%和68.6%（P = 0.003）。ADV添加/ADV单药治疗组的HBeAg累积血清转换率显著高于ETV单药治疗组（P = 0.022）。ETV和ADV单药治疗组分别有6例（25.0%）和6例（13.6%）患者出现病毒突破和基因型耐药，而ADV添加治疗组在开始抗病毒治疗后24个月未出现基因型耐药（P < 0.01）。此外，在ADV添加组中未检测到基因型耐药性。
Background and Aim:There have been no reports comparing the therapeutic results of adefovir (ADV) and entecavir (ETV) rescue therapy for patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB). We aimed to compare the cumulative efficacy and resistance of ETV 1.0 mg monotherapy, ADV monotherapy and ADV add-on LAM combination therapy in LAM-refractory patients.Methods:One hundred and four patients were included in the following three treatment groups; group 1 (n = 24), LAM was switched to ETV (1.0 mg once a day); group 2 (n = 44), LAM was switched to ADV (10 mg once a day); and group 3 (n = 36), ADV was added to LAM (10 mg once a day).Results:After 6 months of rescue treatment, alanine aminotransferase normalization was observed in 75.0%, 65.9% and 74.3% of patients receiving ETV monotherapy, ADV monotherapy and ADV add-on therapy, respectively. A significantly higher log(10)HBV-DNA drop at 6 months occurred in the ADV add-on group compared with the ETV group. The rate of HBV-DNA polymerase chain reaction undetectability (< 300 copies/mL) 6 months after initiation of ETV monotherapy, ADV monotherapy and ADV add-on therapy was 33.3%, 27.3% and 68.6%, respectively (P = 0.003). The cumulative HBeAg seroconversion rate was significantly higher in ADV add-on/ADV monotherapy groups compared with the ETV monotherapy group (P = 0.022). Viral breakthrough and genotypic resistance were detected in six (25.0%) and six (13.6%) patients in the ETV and ADV monotherapy groups, whereas no cases of genotypic resistance were detected in ADV add-on group 24 months after initiation of antiviral treatment (P < 0.01).Conclusion:Adefovir add-on treatment in patients with LAM-resistant CHB suppresses HBV replication more effectively than ETV or ADV monotherapy. Additionally, no genotypic resistance was detected in the ADV add-on group.