恩替卡韦单药治疗与拉米夫定和阿德福韦的从头联合治疗代

StephenW

Entecavir monotherapy versus de novo combination of lamivudine and adefovir for compensated hepatitis B virus-related cirrhosis: a real-world prospective multicenter cohort study

Authors Wu X, Zhou J, Xie W, Ding H, Ou X, Chen G, Ma A, Xu X, Ma H, Xu Y, Liu X, Meng T, Wang L, Sun Y, Wang B, Kong Y, Ma H, You H, Jia J

Received 24 August 2018

Accepted for publication 11 February 2019

Published 1 April 2019 Volume 2019:12 Pages 745—757

DOI https://doi.org/10.2147/IDR.S185120


Editor who approved publication: Professor Suresh Antony

Xiaoning Wu,1–3,* Jialing Zhou,1–3,* Wen Xie,4 Huiguo Ding,5 Xiaojuan Ou,1–3 Guofeng Chen,6 Anlin Ma,7 Xiaoyuan Xu,8 Hui Ma,9 Youqing Xu,10 Xiaoqing Liu,11 Tongtong Meng,1–3 Lin Wang,1–3 Yameng Sun,1–3 Bingqiong Wang,1–3 Yuanyuan Kong,1–3 Hong Ma,1–3 Hong You,1–3 Jidong Jia1–3

1Liver Research Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China; 2Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China; 3National Clinical Research Center of Digestive Diseases, Beijing, China; 4Liver Fibrosis Centre, Beijing Ditan Hospital, Capital Medical University, Beijing, China; 5Department of Digestive Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China; 6Liver Fibrosis Centre, Beijing 302 Hospital, Beijing, China; 7Department of Infectious Diseases, China-Japan Friendship Hospital, Beijing, China; 8Department of Infectious Diseases, Peking University First Hospital, Beijing, China; 9Liver Research Centre, Peking University People’s Hospital, Beijing, China; 10Department of Digestive Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 11Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China

*These authors contributed equally to this work

Background: De novo combination of lamivudine (Lam) and adefovir (Adv) was not rarely used in clinical practice. However, head-to-head comparisons of entecavir (Etv) monotherapy with this combination in hepatitis B virus (HBV)-related compensated cirrhosis patients are unavailable. This study aimed to compare the efficacy and safety of Etv monotherapy with combination therapy in patients with HBV-related compensated liver cirrhosis.
Methods: Treatment-naïve patients with HBV-related compensated liver cirrhosis were recruited to receive either Etv monotherapy or a de novo combination of Lam and Adv. Data were collected at baseline and every 6 months thereafter.
Results: A total of 578 patients (485 in Etv group, 93 in combination group) were included. Baseline characteristics were comparable between the two groups. At the end of 1, 2, and 3 years, HBV DNA was undetectable in 82.7%, 96.2%, and 94.3% of patients in the Etv group and 88.9%, 81.7%, and 84.6% in the combination group, respectively (all P>0.05). The cumulative virological breakthrough rate at 1, 2, and 3 years was 2.7%, 6.7%, and 9.8% in the Etv group and 2.9%, 13.3%, and 32.2% in the combination group, respectively (P=0.003). After propensity-score adjustment for age, sex, and baseline HBeAg, ALT, and total bilirubin, virological breakthrough was higher in the de novo combination of Lam and Adv (HR 2.83, 95% CI 1.37–5.86; P<0.01). The cumulative rate of liver-related events, including decompensation and hepatocellular carcinoma, at 1, 2, and 3 years was 2.9%, 4.2%, and 6.1% in the Etv group and 2.2%, 2.2%, and 6.7% in combination group, respectively (P=0.83). Biochemical response and serological response were similar between the groups.
Conclusion: Etv treatment had less virological breakthrough and potentially higher HBV-DNA suppression than de novo combination of Lam and Adv during 3 years in treatment-naïve HBV-related compensated liver cirrhosis.

Keywords: entecavir, de novo combination, lamivudine, adefovir, compensated HBV-related cirrhosis, real-world, virological breakthrough

StephenW

恩替卡韦单药治疗与拉米夫定和阿德福韦的从头联合治疗代偿性乙型肝炎病毒相关性肝硬化：现实世界前瞻性多中心队列研究

作者吴昕，周杰，谢炜，丁鹤，欧昕，陈庚，马阿，徐昕，马鹤，徐莹，刘昕，孟婷，王璐，孙烨，王蓓，孔莹，马H，You H，Jia J

2018年8月24日收到

接受发表于2019年2月11日

2019年4月1日出版卷2019：12页745-757

DOI https://doi.org/10.2147/IDR.S185120


批准出版的编辑：Suresh Antony教授

吴晓宁，1-3岁，* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *刘晓青，11童同梦，1-3林王，1-3岁的孙亚蒙，1-3王炳琼，1-3袁元刚，1-3马红，1-3红友，1-3冀东佳1-3

首都医科大学附属北京友谊医院1Liver研究中心，北京; 2北京市肝硬化转化医学重点实验室，北京; 3国家消化疾病临床研究中心，北京;首都医科大学附属北京地坛医院4肝纤维化中心，北京; 5首都医科大学附属北京佑安医院消化系，北京;北京302医院6肝纤维化中心，北京; 7中国友好医院感染科，北京; 8北京大学第一医院感染科，北京;北京大学人民医院9人研究中心，北京;首都医科大学附属北京天坛医院10消化系，北京; 11北京协和医院感染科，北京，中国

*这些作者同等贡献这项工作

背景：拉米夫定（Lam）和阿德福韦（Adv）的重新组合在临床实践中并不常用。然而，恩替卡韦（Etv）单药治疗与乙型肝炎病毒（HBV）相关的代偿性肝硬化患者的这种组合的头对头比较是不可用的。本研究旨在比较Etv单药治疗与HBV相关代偿性肝硬化患者联合治疗的疗效和安全性。
方法：招募接受治疗的初治HBV相关代偿性肝硬化患者接受Etv单药治疗或Lam和Adv的从头组合。在基线和之后每6个月收集数据。
结果：共纳入578例患者（Etv组485例，联合组93例）。基线特征在两组之间具有可比性。在1年，2年和3年结束时，Etv组中82.7％，96.2％和94.3％的患者HBV DNA检测不到，组合组分别为88.9％，81.7％和84.6％（均为P> 0.05）。 Etv组在1,2和3年的累积病毒学突破率分别为2.7％，6.7％和9.8％，组合组分别为2.9％，13.3％和32.2％（P = 0.003）。在对年龄，性别和基线HBeAg，ALT和总胆红素进行倾向评分调整后，Lam和Adv的从头组合中病毒学突破较高（HR 2.83,95％CI 1.37-5.86; P <0.01）。 1年，2年和3年肝脏相关事件（包括失代偿和肝细胞癌）的累积率在Etv组为2.9％，4.2％和6.1％，组合组为2.2％，2.2％和6.7％分别（P = 0.83）。各组之间的生化反应和血清学反应相似。
结论：治疗初期HBV相关代偿性肝硬化3年内，Etv治疗的病毒学突破较少，HBV-DNA抑制作用可能高于Lam和Adv的从头组合。

关键词：恩替卡韦，de novo组合，拉米夫定，阿德福韦，代偿性HBV相关性肝硬化，现实世界，病毒学突破