Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection
Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection
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DOI：
10.1086/324003
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发表时间：
2001-11-15
影响因子：
6.4
通讯作者：
Clark, JM
中科院分区：
文献类型：
--
作者：
Colonno, RJ;Genovesi, EV;Clark, JM
恩替卡韦（ETV）是一种鸟苷核苷类似物，对慢性感染土拨鼠肝炎病毒的土拨鼠具有有效的抗病毒疗效。为了探索长期病毒抑制的后果，土拨鼠口服ETV 8周，然后每周一次，持续12个月。在退出治疗并额外监测28个月的6只动物中，3只具有持续的抗病毒应答，并且没有肝细胞癌（HCC）的证据。在继续每周ETV方案额外22个月的6只动物中，4只表现出血清病毒DNA水平接近检测下限>2年，并且没有HCC的证据。所有动物肝脏样本中的病毒抗原和共价闭合环状DNA水平均显著降低。ETV耐受性良好，没有证据表明存在耐药变异。根据历史数据，长期ETV治疗似乎显著延长了治疗动物的寿命，并延迟了HCC的出现。
Entecavir (ETV) is a guanosine nucleoside analogue with potent antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus. To explore the consequences of prolonged virus suppression, woodchucks received ETV orally for 8 weeks and then weekly for 12 months. Of the 6 animals withdrawn from therapy and monitored for an additional 28 months, 3 had a sustained antiviral response and had no evidence of hepatocellular carcinoma (HCC). Of the 6 animals that continued on a weekly ETV regimen for an additional 22 months, 4 exhibited serum viral DNA levels near the lower limit of detection for >2 years and had no evidence of HCC. Viral antigens and covalently closed circular DNA levels in liver samples were significantly reduced in all animals. ETV was well tolerated, and there was no evidence of resistant variants. On the basis of historical data, long-term ETV treatment appeared to significantly prolong the life of treated animals and delay the emergence of HCC.