替诺福韦地索普西富马酸盐在中国慢性乙型肝炎患者中的长

StephenW

Hepatol Int. 2019 Apr 11. doi: 10.1007/s12072-019-09943-6. [Epub ahead of print]
Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results.
Liang X1, Gao Z2, Xie Q3, Zhang J4, Sheng J5, Cheng J6, Chen C7, Mao Q8, Zhao W9, Ren H10, Tan D11, Niu J12, Chen S13, Pan C14, Tang H15, Wang H16, Mao Y17, Jia J18, Ning Q19, Xu M20, Wu S21, Li J22, Zhang X3, Zhang W23, Xiong C23, Hou J24.
Author information

1
    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
2
    3rd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
3
    Ruijin Hospital Affiliated to Jiaotong University, School of Medicine, Shanghai, China.
4
    Huashan Hospital Affiliated to Fudan University, Shanghai, China.
5
    1st Affiliated Hospital of ZheJiang University, Hangzhou, China.
6
    Beijing Ditan Hospital, Capital Medical University, Beijing, China.
7
    Shanghai the 85th Hospital Affiliated to Nanjing Military, Shanghai, China.
8
    Southwest Hospital, Army Medical University, Chongqing, China.
9
    2nd Hospital of Nanjing, Nanjing, China.
10
    2nd Affiliated Hospital Chongqing Medical University, Chongqing, China.
11
    Xiangya Hospital Central-South University, Changsha, China.
12
    1st Affiliated Hospital of Jilin University, Changchun, China.
13
    Jinan Hospital for Infectious Disease, Jinan, China.
14
    Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian Sheng, China.
15
    West China Hospital, Sichuan University, Chengdu, China.
16
    Peking University People's Hospital, Beijing, China.
17
    RenJi Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
18
    Beijing Friendship Hospital, Capital University, Beijing, China.
19
    Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
20
    Guangzhou Eighth Municipal People's Hospital, Guangzhou, China.
21
    Shanghai Public Health Clinical Center, Shanghai, China.
22
    The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
23
    GlaxoSmithKline R&D Company Limited, Shanghai, China.
24
    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. [email protected].

Abstract
BACKGROUND AND AIM:

Long-term treatment with tenofovir disoproxil fumarate (TDF) has demonstrated suppression of viral replication outside of China. This study aims to assess efficacy, resistance and safety of TDF for up to 240 weeks in Chinese patients with chronic hepatitis B virus (HBV) infection.
METHODS:

Patients (HBeAg-positive or HBeAg-negative) who were randomised to receive TDF 300 mg or adefovir dipivoxil (ADV) 10 mg once daily in the 48-week double-blind phase (N = 498) were eligible to enter the open-label TDF phase (TDF-TDF and ADV-TDF groups) for additional 192 weeks.
RESULTS:

Overall, 457/512 (89.3%) randomised patients completed 240 weeks of treatment. Virological suppression was achieved in 84.5% and 87.9% in HBeAg-positive patients and 89.6% and 89.5% in HBeAg-negative patients in TDF-TDF and ADV-TDF groups, respectively, at week 240. The majority of patients from both groups had normalized alanine transaminase levels. More patients had HBeAg loss (41.7% vs. 36.4%) and HBeAg seroconversion (32.0% vs. 28.3%) in TDF-TDF than in ADV-TDF group, respectively. Only one HBeAg-positive patient in TDF-TDF group had HBsAg loss at week 240. No evidence of resistance to TDF was observed. The incidence of adverse events was similar in both groups (TDF-TDF, 56.4% vs. ADV-TDF, 51.6%). One patient had serum creatinine elevation ≥ 0.5 mg/dL above baseline, and three patients had confirmed grade 3/4 phosphorus abnormalities (< 2 mg/dL).
CONCLUSION:

In Chinese patients with chronic HBV, long-term treatment with TDF showed sustained viral suppression without development of resistance up to 240 weeks. No new safety concerns were found with TDF in this patient population. Clinical Trial Registration ClinicalTrial.gov Identifier NCT01300234; GSK Clinical Study Register 114648.
KEYWORDS:

Antiviral therapy; Chronic hepatitis B; Long-term tenofovir disoproxil fumarate; Virological suppression

PMID:
    30977033
DOI:
    10.1007/s12072-019-09943-6

StephenW

Hepatol Int。 2019年4月11日doi：10.1007 / s12072-019-09943-6。 [印刷前的电子版]
替诺福韦地索普西富马酸盐在中国慢性乙型肝炎患者中的长期疗效和安全性：5年结果。
Liang X1，Gao Z2，Xie Q3，Zhang J4，Sheng J5，Cheng J6，Chen C7，Mao Q8，Zhao W9，Ren H10，Tan D11，Ni J12，Chen S13，Pan C14，Tang H15，Wang H16，Mao Y17 ，贾J18，宁Q19，徐M20，吴S21，李J22，张X3，张W23，熊C23，侯J24。
作者信息

1
    南方医科大学南方医院肝病科，传染病科，广东省病毒性肝炎研究重点实验室器官衰竭研究国家重点实验室，广州510515
2
    中山大学附属第三医院，广州，中国。
3
    上海交通大学附属瑞金医院，上海。
4
    复旦大学附属华山医院，中国上海。
五
    浙江大学第一附属医院，杭州，中国。
6
    首都医科大学附属北京地坛医院，中国北京。
7
    上海南京军区附属第85医院，中国上海。
8
    中国重庆市陆军医科大学西南医院。
9
    南京第二医院，南京，中国。
10
    重庆医科大学附属第二医院，重庆，中国。
11
    中南大学湘雅医院，长沙，中国。
12
    吉林大学第一附属医院，长春，中国。
13
    济南市传染病医院，济南，中国。
14
    福建医科大学孟超肝胆外科医院，福建省，中国。
15
    四川大学华西医院，中国成都。
16
    北京大学人民医院，中国北京。
17
    上海交通大学医学院仁济医院，上海
18
    首都大学北京友谊医院，中国北京。
19
    华中科技大学同济医学院同济医院，武汉
20
    广州市第八人民医院，广州，中国。
21
    上海市公共卫生临床中心，中国上海。
22
    南京医科大学附属第一医院，中国南京。
23
    葛兰素史克研发有限公司，中国上海。
24
    南方医科大学南方医院肝病科，传染病科，广东省病毒性肝炎研究重点实验室器官衰竭研究国家重点实验室，广州510515 [email protected]。

抽象
背景和目的：

使用替诺福韦地索普西富马酸盐（TDF）进行长期治疗已证实可抑制中国境外的病毒复制。本研究旨在评估中国慢性乙型肝炎病毒（HBV）感染患者TDF长达240周的疗效，耐药性和安全性。
方法：

在48周双盲期（N = 498）中随机接受TDF 300 mg或阿德福韦酯（ADV）10 mg每日一次的患者（HBeAg阳性或HBeAg阴性）有资格进入开放标签TDF阶段（TDF-TDF和ADV-TDF组）额外192周。
结果：

总体而言，457/512（89.3％）随机患者完成了240周的治疗。 HBeAg阳性患者的病毒学抑制率分别为84.5％和87.9％，TDF-TDF和ADV-TDF组的HBeAg阴性患者分别为89.6％和89.5％，两周均有病毒抑制。标准化的丙氨酸转氨酶水平。 TDF-TDF患者的HBeAg丢失率（41.7％vs。36.4％）和HBeAg血清学转换率（32.0％vs。28.3％）分别高于ADV-TDF组。 TDF-TDF组中只有一名HBeAg阳性患者在240周时出现HBsAg消失。未观察到对TDF耐药的证据。两组的不良事件发生率相似（TDF-TDF，相对于ADV-TDF为56.4％，51.6％）。一名患者的血清肌酐升高≥5.5mg / dL高于基线，3名患者确认3/4级磷异常（<2 mg / dL）。
结论：

在中国慢性HBV患者中，TDF长期治疗显示持续的病毒抑制而不会产生长达240周的耐药性。在该患者群体中没有发现TDF的新安全性问题。临床试验注册ClinicalTrial.gov标识符NCT01300234; GSK临床研究登记表114648。
关键词：

抗病毒治疗;慢性乙型肝炎;长效替诺福韦地索普西富马酸盐;病毒学抑制

结论：
    30977033
DOI：
    10.1007 / s12072-019-09943-6

StephenW

https://link.springer.com/conten ... 072-019-09943-6.pdf