Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Gravendijkwal 230, Room Ha 204, Rotterdam, The Netherlands.
J Hepatol. 2010 Apr;52(4):493-500. doi: 10.1016/j.jhep.2010.01.012. Epub 2010 Feb 4.
BACKGROUND & AIMS: Entecavir is a potent inhibitor of viral replication in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B patients, but data on the efficacy in NA-experienced subjects are limited.
In a multi-center cohort study we investigated 161 chronic hepatitis B patients (34% NA-experienced) treated with entecavir monotherapy.
During a median follow-up of 11 (3-23)months, 82 (79%) of 104 NA-naïve patients achieved virologic response (VR), defined as HBV DNA <80IU/ml, and none of the patients (0%) developed genotypic entecavir-resistance. VR was demonstrated in 31 (54%) of 57 NA-experienced patients during a median follow-up of 12 (3-31)months. Patients with lamivudine-resistant mutations at the start of entecavir monotherapy had a reduced probability of achieving VR compared to lamivudine-naïve patients (HR 0.14; 95% CI 0.04-0.58; p=0.007). Antiviral efficacy was not decreased by prior treatment with lamivudine when lamivudine-resistance had never developed (HR 0.81; 95% CI 0.43-1.52; p=0.52). Prior adefovir therapy without development of adefovir-resistance (HR 0.84; 95% CI 0.43-1.64; p=0.61) and presence of adefovir-resistance (HR 0.86; 95% CI 0.27-2.71; p=0.80) did not influence antiviral response to entecavir. Switching to a tenofovir-containing treatment regimen resulted in viral load decline in patients with entecavir-resistance associated mutations.
Entecavir proved to be efficacious in NA-naïve patients. The antiviral efficacy of entecavir was not influenced by prior treatment with adefovir or presence of adefovir-resistance. Entecavir should not be used in patients with previous lamivudine-resistance, yet it may still be an option in lamivudine-experienced patients in case lamivudine-resistance never developed.
恩替卡韦是一种强效的核苷酸类似物（NA）初治慢性乙型肝炎患者病毒复制抑制剂，但在 NA 经治患者中的疗效数据有限。
我们在一项多中心队列研究中调查了 161 例接受恩替卡韦单药治疗的慢性乙型肝炎患者（34%为 NA 经治）。
在中位随访 11（3-23）个月期间，104 例 NA 初治患者中有 82 例（79%）达到病毒学应答（VR），定义为 HBV DNA <80IU/ml，且无患者（0%）发生基因型恩替卡韦耐药。在中位随访 12（3-31）个月期间，57 例 NA 经治患者中有 31 例（54%）达到 VR。恩替卡韦单药治疗起始时存在拉米夫定耐药突变的患者与拉米夫定初治患者相比，达到 VR 的可能性降低（HR 0.14；95%CI 0.04-0.58；p=0.007）。当从未发生拉米夫定耐药时，先前用拉米夫定治疗并未降低抗病毒疗效（HR 0.81；95%CI 0.43-1.52；p=0.52）。阿德福韦耐药（HR 0.86；95%CI 0.27-2.71；p=0.80）或无阿德福韦耐药（HR 0.84；95%CI 0.43-1.64；p=0.61）的阿德福韦既往治疗并未影响恩替卡韦的抗病毒反应。对存在恩替卡韦耐药相关突变的患者换用含替诺福韦的治疗方案可导致病毒载量下降。
恩替卡韦在 NA 初治患者中证明是有效的。阿德福韦既往治疗或阿德福韦耐药的存在并不影响恩替卡韦的抗病毒疗效。对于先前有拉米夫定耐药的患者，不应使用恩替卡韦，但对于从未发生拉米夫定耐药的拉米夫定经治患者，恩替卡韦仍可能是一种选择。
