Ha Minghao, Zhang Guotong, Diao Shu, Lin Mingfang, Wu Jianqiu, Sun Liping, She Huiyuan, Shen Lihui, Huang Chunhong, Shen Wenjuan, Huang Zhongming
Department of Infectious Diseases and Hepatology, Shanghai 7th People's Hospital, China.
Intern Med. 2012;51(12):1509-15. doi: 10.2169/internalmedicine.51.7329. Epub 2012 Jun 15.
We aimed to compare the cumulative efficacy and resistance of ADV monotherapy, ADV add-on LAM (ADV + LAM), ADV and ETV (ADV + ETV) combination therapy in LAM-resistant patients.
Ninety-one adult CHB patients with LAM-resistance mutations (YMDD) were identified. Of these 91, 29 patients were treated with ADV monotherapy, 30 were treated with ADV + LAM and 32 were treated with ADV + ETV combination therapy, for at least 24 months.
The mean serum HBV-DNA decreases from baseline at 3, 6, 12, and 24 months were -3.23, -4.41, -5.32, and -5.58 log(10) IU/mL in the ADV + ETV combination therapy groups, respectively; the most significant among the three treatment groups (p<0.01). The rate of HBV-DNA PCR undetectability (<60 IU/mL) at 6 months in ADV + ETV combination therapy was 78.1%; also the most significant among the three treatment groups (p=0.024). Viral breakthrough and genotypic mutations were detected in 8 (27.6%) and 4 (13.3%) patients in the ADV monotherapy and ADV+LAM therapy groups, respectively; whereas no case of viral breakthrough and genotypic resistance was detected in the ADV+ETV combination therapy group after 24 months (p<0.05).
ADV + ETV combination therapy demonstrated faster and significantly greater suppression of HBV DNA compared with ADV add-on LAM combination therapy for patients with LAM-resistance mutations. ADV + ETV was superior to ADV + LAM in achieving initial virological response and long-term suppression activity against HBV. ADV + ETV combination therapy was the most effective to refrain from selecting HBV strains with cross-resistance to three NAs (LAM, ADV and ETV) for LAM-resistance patients.
我们旨在比较阿德福韦酯（ADV）单药治疗、阿德福韦酯联合拉米夫定（ADV + LAM）、阿德福韦酯与恩替卡韦（ADV + ETV）联合治疗对拉米夫定耐药患者的累积疗效和耐药情况。
确定91例伴有拉米夫定耐药突变（YMDD）的成年慢性乙型肝炎（CHB）患者。这91例患者中，29例接受阿德福韦酯单药治疗，30例接受阿德福韦酯联合拉米夫定治疗，32例接受阿德福韦酯与恩替卡韦联合治疗，治疗时间至少24个月。
阿德福韦酯与恩替卡韦联合治疗组在3、6、12和24个月时血清乙肝病毒（HBV）-DNA较基线的平均下降值分别为-3.23、-4.41、-5.32和-5.58 log(10) IU/mL；在三个治疗组中下降最为显著（p<0.01）。阿德福韦酯与恩替卡韦联合治疗组在6个月时HBV-DNA PCR检测不到（<60 IU/mL）的比例为78.1%；在三个治疗组中也最为显著（p = 0.024）。阿德福韦酯单药治疗组和阿德福韦酯联合拉米夫定治疗组分别有8例（27.6%）和4例（13.3%）患者检测到病毒突破和基因变异；而阿德福韦酯与恩替卡韦联合治疗组在24个月后未检测到病毒突破和基因耐药病例（p<0.05）。
对于伴有拉米夫定耐药突变的患者，与阿德福韦酯联合拉米夫定治疗相比，阿德福韦酯与恩替卡韦联合治疗对HBV DNA的抑制作用更快且显著更强。在实现初始病毒学应答和对HBV的长期抑制活性方面，阿德福韦酯与恩替卡韦联合治疗优于阿德福韦酯联合拉米夫定治疗。对于拉米夫定耐药患者，阿德福韦酯与恩替卡韦联合治疗在避免选择对三种核苷（拉米夫定、阿德福韦酯和恩替卡韦）产生交叉耐药的HBV毒株方面最为有效。
