de Man R A, Wolters L M, Nevens F, Chua D, Sherman M, Lai C L, Gadano A, Lee Y, Mazzotta F, Thomas N, DeHertogh D
Erasmus University Hospital, Rotterdam, The Netherlands.
Hepatology. 2001 Sep;34(3):578-82. doi: 10.1053/jhep.2001.26815.
Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log(10) reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P <.05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients.
恩替卡韦是一种对乙型肝炎病毒（HBV）具有选择性活性的口服抗病毒药物。我们对慢性乙型肝炎感染患者进行了一项随机、安慰剂对照、剂量递增研究，在该研究中我们评估了恩替卡韦治疗28天的疗效和安全性。随访期为24周。所有剂量的恩替卡韦（0.05毫克、0.1毫克、0.5毫克和1.0毫克）均显示出对HBV复制的显著抑制，病毒载量平均对数（10）分别降低2.21、2.29、2.81和2.55。接受恩替卡韦治疗的患者中约25%的人HBV DNA下降至Chiron HBV - DNA检测法的检测下限以下（<0.7 MEq/mL）。在给药后的随访期内，与接受较低剂量治疗的患者相比，接受0.5毫克和1.0毫克恩替卡韦治疗的患者其HBV DNA水平恢复至基线的速度明显较慢（P<.05）。所有剂量的恩替卡韦耐受性良好，治疗患者与接受安慰剂治疗的患者之间无显著差异。在剂量组和安慰剂组中，未观察到基线至治疗结束时丙氨酸转氨酶（ALT）水平有显著变化。三名患者（9%）（0.05毫克、0.1毫克和0.5毫克组各1例）在停用恩替卡韦后16周（2例患者）和24周（1例患者）出现无症状肝炎发作。总之，在这项为期28天的恩替卡韦研究中，观察到HBV DNA明显下降，与接受安慰剂治疗的患者相比，恩替卡韦治疗的患者无显著副作用。
