富马酸替诺福韦二吡呋酯治疗多种核苷（酸）类似物治疗失

StephenW

富马酸替诺福韦二吡呋酯治疗多种核苷（酸）类似物治疗失败乙型肝炎：单药治疗是否足够？
协二良1、清解2、贾尚3、洪塘4、徐敏5、清华萌6、张继明7、高朴军8、吉芳生9、王浩10、冀东佳11、王桂强12、吴顺全13、京南坪13、金林侯1
隶属关系
隶属关系

    1
    南方医科大学南方医院，广州，中国。
    2
    上海交通大学医学院附属瑞金医院。
    3
    河南省人民医院感染科，郑州，中国。
    4
    四川大学华西医院，四川，成都，中国。
    5
    广州市第八人民医院，广州，中国。
    6
    首都医科大学北京佑安医院，北京，中国。
    7
    复旦大学附属华山医院，上海，中国。
    8
    吉林大学第一医院，吉林，长春，中国。
    9
    浙江大学医学院附属第一医院传染病诊疗协同创新中心感染科，杭州，中国。
    10
    北京大学人民医院，北京，中国。
    11
    首都医科大学北京友谊医院，北京，中国。
    12
    北京大学第一医院，北京，中国。
    13
    中国上海葛兰素史克研发有限公司。

    PMID：34894002 DOI：10.1111/jgh.15757

抽象的

背景与目的：富马酸替诺福韦二吡呋酯（TDF）因其高效力和低耐药率而成为慢性乙型肝炎病毒（HBV）感染的一线治疗药物。本研究调查了 TDF 在使用多种核苷（酸）类似物（NAs）治疗失败后慢性乙型肝炎（CHB）感染的中国患者中的疗效和安全性。

方法：患者包括：年龄 18-65 岁，多次 NA 治疗失败（≥ 2 种不同 NA 治疗后血清 HBV DNA >200 IU/mL）。主要终点是在 TDF 单药治疗第 144 周时血清 HBV DNA <20 IU/mL 的患者比例。还评估了次要终点和安全性。

结果：总共招募了 213 名患者。在第 144 周时，平均 HBV DNA 比基线显着降低（4.4 vs 1.4 log10 IU/mL），77.0% 的患者（95% CI：71.1, 82.9）达到血清 HBV DNA <20 IU/mL。三名 (1.4%) 患者在 TDF 单药治疗期间经历了病毒学突破，没有肝炎发作。在第 144 周，分别有 15.3% 和 4.7% 的患者（基线时 HBeAg 阳性）出现乙型肝炎 e 抗原（HBeAg）消失和 HBeAg 血清学转换； 68.3% 的患者达到了正常的丙氨酸转氨酶水平。总体而言，58.7% 的患者经历了≥1 次 AE。最常见的 AE 是上呼吸道感染和血肌酸磷酸激酶升高； 8.5% 的患者经历了与研究药物相关的 AE； 9.4% 的患者经历了严重的 AE（没有一个与 TDF 相关）。在肾脏安全参数中，平均血清磷水平的总体趋势保持稳定，而平均估计肾小球滤过率略有增加。

结论：TDF 单药治疗对多次 NAs 治疗失败的 CHB 患者有效，没有新的安全性发现。

关键词：抗病毒性；中国;功效;乙型肝炎e抗原；乙型肝炎表面抗原；乙型肝炎病毒;乙型肝炎病毒耐药性；多重耐药性；安全;病毒学反应。

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StephenW

Tenofovir disoproxil fumarate for multiple nucleos(t)ide analogues treatment failure hepatitis B: is monotherapy enough?
Xieer Liang  1 , Qing Xie  2 , Jia Shang  3 , Hong Tang  4 , Min Xu  5 , Qinghua Meng  6 , Jiming Zhang  7 , Pujun Gao  8 , Jifang Sheng  9 , Hao Wang  10 , Jidong Jia  11 , Guiqiang Wang  12 , Shunquan Wu  13 , Jingna Ping  13 , Jinlin Hou  1
Affiliations
Affiliations

    1
    Nanfang Hospital, Southern Medical University, Guangzhou, China.
    2
    Ruijin Hospital Affiliated to Jiaotong University, School of Medicine, Shanghai, China.
    3
    Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China.
    4
    West China Hospital of Sichuan University, Sichuan, Chengdu, China.
    5
    Guangzhou Eighth Municipal People's Hospital, Guangzhou, China.
    6
    Beijing You-An Hospital, Capital Medical University, Beijing, China.
    7
    Huashan Hospital Affiliated to Fudan University, Shanghai, China.
    8
    The First Hospital of Jilin University, Jilin, Changchun, China.
    9
    Department of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
    10
    Peking University People's Hospital, Beijing, China.
    11
    Beijing Friendship Hospital, Capital Medical University, Beijing, China.
    12
    Peking University First Hospital, Beijing, China.
    13
    GlaxoSmithKline R&D Company Limited, Shanghai, China.

    PMID: 34894002 DOI: 10.1111/jgh.15757

Abstract

Background and aim: Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs).

Methods: Patients included were: aged 18-65 years, with treatment failure with multiple NAs (serum HBV DNA >200 IU/mL after ≥2 different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA <20 IU/mL at Week 144 of TDF monotherapy. Secondary endpoints and safety were also assessed.

Results: Overall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 log10 IU/mL), with 77.0% patients (95% CI: 71.1, 82.9) achieving serum HBV DNA <20 IU/mL. Three (1.4%) patients experienced virological breakthrough during TDF monotherapy, without hepatitis flare. At Week 144, 15.3% and 4.7% patients (HBeAg-positive at baseline) experienced hepatitis B e antigen (HBeAg) loss and HBeAg seroconversion, respectively; 68.3% patients achieved normalized alanine aminotransferase levels. Overall, 58.7% patients experienced ≥1 AE. Most common AEs were upper respiratory tract infection and blood creatine phosphokinase increase; 8.5% patients experienced study drug-related AEs; 9.4% patients experienced serious AEs (none were TDF-related). Among renal safety parameters, overall trend of mean serum phosphorous level remained stable, while mean estimated glomerular filtration rate increased slightly.

Conclusions: TDF monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.

Keywords: Antiviral resistance; China; efficacy; hepatitis B e antigen; hepatitis B surface antigen; hepatitis B virus; hepatitis B virus resistance; multidrug-resistance; safety; virological response.

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