拉米夫定，阿德福韦，并结合在HBeAg阳性慢性乙型肝炎的随机

StephenW

http://www.ncbi.nlm.nih.gov/pubmed/23069315
Clin Res Hepatol Gastroenterol. 2012 Oct 12. pii: S2210-7401(12)00173-8. doi: 10.1016/j.clinre.2012.05.012. [Epub ahead of print]
Randomized trial of lamivudine, adefovir, and the combination in HBeAg-positive chronic hepatitis B.
He Z, Wang J, Liu K, Huang H, Du Y, Lin Z, Cai M, Feng X.
Source

Department of Infectious Diseases, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China. Electronic address: [email protected].
Abstract

The aim of this study was to compare the efficacy of lamivudine or adefovir alone for 96weeks versus initial treatment with the combination of lamivudine and adefovir for 12 to 24weeks followed by adefovir alone. One hundred and fifty patients with HBeAg-positive chronic hepatitis B were randomized equally to lamivudine and adefovir diprivoxil combination therapy (LA), lamivudine alone (L), or adefovir dipivoxil alone (A) in a multicenter randomized clinical trial. In the LA group, the earliest time for lamivudine discontinuation was 12weeks and adefovir monotherapy was continued until 96weeks. Groups L and A received monotherapies for 96weeks. At 12weeks, the decrease in HBV DNA, percentage of patients with negative HBV DNA, and ALT normalization rate for the LA group were comparable to those of group L, but superior to those of group A. At 24weeks, the rates of negative HBV DNA and HBeAg seroconversion of group LA were significantly higher than the monotherapy groups. This superiority was subsequently preserved during the maintenance phase with adefovir monotherapy. Starting at 48weeks, the mean HBV DNA level of group L increased over the 24-week level. In contrast, the A group's rates of virological response, biochemical response, and HBeAg seroconversion continued to improve. At week 96, the percentage of patients with undetectable DNA and HBe seroconversion of LA group (100%, 51%) was higher than that of L (66%, 21%) and A group (49%, 33%), while no significant difference was observed between the L and A groups. During the course of therapy, no lamivudine- or adefovir-resistance mutations were discovered in the LA group. Rates of adverse reactions were comparable between the three groups. Combination therapy with lamivudine and adefovir for 12 to 24weeks followed by adefovir monotherapy significantly improved antiviral efficacy and reduced drug resistance without compromising safety and tolerability compared to either drug alone in HBeAg-positive chronic hepatitis B.

StephenW

传染科，上海，复旦大学，上海200240，中国第五人民医院。电子地址：[email protected]。

本研究的目的是与最初的治疗与拉米夫定联合阿德福韦12-24周阿德福韦单独的疗效比较拉米夫定或阿德福韦单独96周。 150例HBeAg阳性慢性乙型肝炎患者随机同样拉米夫定和阿德福韦diprivoxil的联合治疗（LA），单用拉米夫定（L），或仅阿德福韦酯（A）在一项多中心随机临床试验。在LA组，拉米夫定停药的最早时间是12周，并一直持续到96周阿德福韦酯单药治疗。组L和A单一疗法为96周。在12周，减少HBV DNA，HBV DNA阴性的患者比例，ALT复常率的LA组相比，L组，但优于A组在24周，HBV DNA阴性率LA组的HBeAg血清转换率明显高于单药治疗组。随后，这个优势是保留在维护阶段，阿德福韦酯单药治疗。从在48周，L组的HBV DNA平均水平增加了24周的水平。相比之下，A组的病毒学反应，生化反应，和HBeAg血清学转换率不断提高。在96周时，检测不到DNA LA组（100％，51％）和HBe血清转换的患者比例明显高于L（66％，21％）和A组（49％，33％），而没有L和A组之间观察到显着差异。在治疗的过程中，没有拉米夫定或阿德福韦耐药突变被发现在洛杉矶。不良反应率分别为三组之间的比较。拉米夫定和阿德福韦联合治疗12-24周阿德福韦酯单药治疗显着提高不妥协的安全性和耐受性相比，无论是单药治疗HBeAg阳性慢性乙型肝炎的抗病毒疗效和耐药性降低