Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection
Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection
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DOI：
10.1053/gast.2002.37058
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发表时间：
2002-12-01
期刊：
影响因子：
29.4
通讯作者：
Dehertogh, D
中科院分区：
文献类型：
--
作者：
Lai, CL;Rosmawati, M;Dehertogh, D
背景与目的：恩替卡韦是一种新型的选择性核苷类似物，具有较强的抗乙肝病毒活性。方法：在为期24周的随机、双盲、多中心、II期临床试验中，比较恩替卡韦(0.01 mg/d、0.1 mg/d、0.5 mg/d)与拉米夫定(100 mg/d)的安全性和有效性。对169例慢性感染乙肝病毒(HBe抗原阳性和阴性)患者的疗效进行了评估。结果：与拉米夫定相比，恩替卡韦在0.1 mg/d剂量组和0.5 mg/d剂量组分别使HBVDNA减少0.97log(10)和1.28log(10)(P<；0.0001)。恩替卡韦存在明显的剂量-反应关系，剂量越高，病毒抑制作用越强。在每天服用恩替卡韦0.5毫克的患者中，83.7%的患者的乙肝病毒脱氧核糖核酸水平低于定量分支脱氧核糖核酸检测的下限(拜耳-Versant诊断公司，以前的ChIron诊断公司，加利福尼亚州埃默里维尔)，相比之下，每天服用100毫克拉米夫定的患者中有57.5%的患者的乙肝病毒脱氧核糖核酸水平低于检测下限(P=0.008)。在两个治疗组中，很少有患者在22周前实现HBeAg丢失和/或血清转换。与拉米夫定相比，接受0.1 mg/d和0.5 mg/d恩替卡韦治疗的患者在22周时丙氨酸转氨酶(ALT)水平恢复正常的患者更多(P=0.05)。恩替卡韦耐受性良好；大多数不良反应是轻微到中度的，短暂的，在所有研究组中具有可比性。结论：恩替卡韦0.1 mg/d和0.5 mg/d剂量对慢性乙肝患者有较强的抗病毒活性，均优于拉米夫定。
Background & Aims: Entecavir is a novel and selective nucleoside analogue with potent activity against hepatitis B virus (HBV). Methods: In a 24-week, double-blind, randomized, multicenter, phase II clinical trial, the safety and efficacy of entecavir (0.01 mg/day, 0.1 mg/day, or 0.5 mg/day orally) were compared with lamivudine (100 mg/day orally). Patients (n = 169) chronically infected with HBV (hepatitis B e antigen [HBeAg]-positive and -negative) were evaluated for efficacy. Results: Compared with lamivudine, entecavir reduced HBV DNA by an additional 0.97 log(10) at the 0.1-mg/day dose and an additional 1.28 log(10),at the 0.5-mg/day dose (P < 0.0001). A clear dose-response relationship was observed for entecavir with the higher doses showing significantly greater viral suppression. In patients treated with entecavir 0.5 mg/day, 83.7% had an HBV-DNA level below the lower limit of detection of the Quantiplex branched DNA (bDNA) assay (Bayer-Versant Diagnostics, formerly Chiron Diagnostics, Emeryville, CA), compared with 57.5% treated with 100 mg/day lamivudine (P = 0.008). In both treatment arms, very few patients achieved HBeAg loss and/or seroconversion by week 22. More patients treated with the 0.1-mg/day and 0.5-mg/day doses of entecavir had normalization of alanine transaminase (ALT) levels at week 22 compared with lamivudine (P = not significant). Entecavir was well tolerated; most adverse events were mild to moderate, transient, and comparable in all study arms. Conclusions: This study showed that entecavir has potent antiviral activity against HBV at 0.1-mg/day and 0.5-mg/day doses, both of which were superior to lamivudine in chronically infected HBV patients.