恩替卡韦和拉米夫定治疗慢性乙型肝炎二年病毒学、血清学和生化结果的随机对比研究

Virologic,serologic and biochemical outcomes through 2 years of treatment with entecavir and lamivudine in nucleoside-naive Chinese patients with chronic hepatitis B:a randomized,multicenter study

目的比较恩替卡韦(ETV)和拉米夫定(LVD)初治慢性乙型肝炎(CHB)患者2年的疗效和安全性。方法519例核苷类似物初治CHB患者随机分别接受ETV(0.5 mg/d)或LVD(1110 mg/d)治疗,第一阶段疗程52周。在48周时获得综合应答的患者于52周停止治疗并随访。在48周时获得部分应答的患者将继续双盲治疗至96周。评估患者HBV DNA水平、丙氨酸氨基转移酶(ALT)复常、血清学标志和安全性方面的情况,并且对基线时HBeAg(+)患者评估HBeAg转阴和血清转换。结果共338例患者进入96周治疗,其中ETV组193例,LVD组145例。疗程结束时,ETV组有74%患者HBV DNA测不出(<300拷贝/ml),96%患者ALT复常。LVD组HBV DNA测不出和ALT复常率分别为41%和82%。ETV组和LVD组实现HBeAg血清学转换的比例分别为11%和19%。总计2年内所有经治患者HBV DNA的累计转阴率ETV组为79%,LVD组为46%(P<0.0001)。两组的不良事件和安全性特征相当。结论初治患者中,ETV治疗96周的HBV DNA抑制率和ALT复常率优于LVD,而两者的安全性相当。

Objective 48 weeks treatment with entecavir has shown superior virologic and biochemical benefit over lamivudine in nucleoside-naive Chinese patients with chronic hepatitis B （CHB）. In this report, entecavir and lamivudine treatment were evaluated though 96 weeks. Methods Chinese adults （n = 519） with CHB were randomized to a minimum of 52 weeks of treatment with entecavir 0.5 mg/d or lamivudine 100 mg/d. Patients with a Consolidated Response at week 48 [HBV DNA 0.7 MEq/ml for ≥24 weeks, ALT 〈1.25 × ULN and, if HBeAg（ ＋ ） at baseline, loss of HBeAg for at least 24 weeks] stopped treatment at week 52 and were followed off-treatment. Patients with a Partial Response at week 48 （ HBV DNA d0.7 MEq/ml in the absence of other criteria for a consolidated response） could continue blinded treatment for up to 96 weeks. Patients were assessed for HBV DNA, ALT normalization, safety, and if HBeAg（ ＋ ） at baseline for HBeAg seroconvesion. Cumulative proportions of all-treated patients who ever achieved these responses were also analyzed. Results Among patients treated during year 2 （enteeavir n = 193; lamivudine n = 145）, 74% of entecavir- and 41% of lamivudine-treated patients had HBV DNA 〈300 copies/ml by PCR at end of dosing （EOD） and 96%o of enteeavir- and 82% of lamivudine-treated patients normalized ALT. 11% of entecavirversus 19% of lamivudine-treated patients underwent HBeAg seroconversion during year 2. Cumulative confirmed analysis for all treated patients through 96 weeks showed that 79% of enteeavir- versus 46% of lamivudine-treated patients （P〈0. 000 1 ） achieved HBV DNA%300 copies/ml by PCR. Similar proportions of enteeavir- and lamivudine-treated patients achieved confirmed ALT normalization and HBeAg seroconversion. Safety profile was comparable in both treatment group. Condusion Among nucleoside naive Chinese patients with CHB, 96 weeks of enticavir treatment results in continued clinical benefit and the safety profile is comparable to lamivudine.