Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304, USA.
Dig Dis Sci. 2012 Nov;57(11):3011-6. doi: 10.1007/s10620-012-2402-2. Epub 2012 Sep 26.
Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients.
We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ≥12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir).
All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir.
Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.
尽管恩替卡韦具有高效性，但仍有相当一部分接受治疗的患者仅获得部分病毒抑制。我们的目标是研究在这些患者中使用替代疗法获得完全病毒抑制（HBV DNA PCR 水平不可检测）的比例。
我们回顾性研究了在三个诊所接受挽救治疗的 42 例恩替卡韦部分应答（治疗 12 个月以上时 HBV DNA 可检测）患者：恩替卡韦+阿德福韦（n=5）、替诺福韦（n=6）和恩替卡韦+替诺福韦（n=31）。通过阴性突变分析和/或无病毒学突破（从最低点增加>1log10IU/mL）排除抗病毒耐药。
所有患者均为亚洲人，57%为男性，中位年龄 36（22-64）岁。仅有少数患者（7%）曾接触过拉米夫定或阿德福韦。几乎所有患者（95%）均为 HBeAg 阳性。在恩替卡韦部分应答者接受挽救治疗 6 个月后，总完全病毒抑制率为 79%，丙氨酸氨基转移酶正常化率为 83%。在恩替卡韦+阿德福韦、替诺福韦和恩替卡韦+替诺福韦治疗组中，6 个月和 12 个月时的完全病毒抑制累积率有显著差异（P=0.0164）（分别为 20%、83%和 83%；20%、100%和 97%）。在恩替卡韦+阿德福韦治疗中未完全病毒抑制的 3 例患者，在转为恩替卡韦+替诺福韦治疗 6 个月后均转为无病毒血症。
恩替卡韦+替诺福韦联合治疗和替诺福韦单药治疗在大多数患者中似乎具有相似的病毒学应答，但与恩替卡韦+阿德福韦联合治疗不同。
