Monotherapy with tenofovir disoproxil fumarate for adefovir-resistant vs. entecavir-resistant chronic hepatitis B: A 5-year clinical trial

阿德福韦 恩替卡韦 医学 内科学 胃肠病学 乙型肝炎表面抗原 拉米夫定 联合疗法 HBeAg 人口 乙型肝炎病毒 乙型肝炎 病毒学 病毒 环境卫生
作者
Young Suk Lim,Geum Youn Gwak,Jonggi Choi,Yung Sang Lee,Kwan Soo Byun,Yoon Jun Kim,Byung Chul Yoo,So Young Kwon,Han Chu Lee
出处
期刊:Journal of Hepatology [Elsevier BV]
卷期号:71 (1): 35-44 被引量:30
标识
DOI:10.1016/j.jhep.2019.02.021
摘要

•240 weeks of TDF monotherapy provided an increasing virologic response rate in patients with multidrug-resistant HBV. •Virologic breakthrough was rare and not associated with emergence of additional resistance mutations. •The HBeAg seroconversion rate was very low and no patient achieved HBsAg seroclearance up to week 240. •Prolonged continuous treatment may be needed to maintain viral suppression in these patients. •Progressive and significant decreases in renal function and bone mineral density after week 144 raise safety concerns. Background & Aims Tenofovir disoproxil fumarate (TDF) monotherapy has displayed non-inferior efficacy to TDF plus entecavir (ETV) combination therapy in patients with hepatitis B virus (HBV) resistant to ETV and/or adefovir (ADV). Nonetheless, the virologic response rate was suboptimal in patients receiving up to 144 weeks of TDF monotherapy. We aimed to assess the efficacy and safety of TDF monotherapy given for up to 240 weeks. Methods One trial enrolled patients with ETV resistance without ADV resistance (n = 90), and another trial included patients with ADV resistance (n = 102). Most patients (91.2%) also had lamivudine resistance. Patients were randomized 1:1 to receive TDF monotherapy or TDF + ETV combination therapy for 48 weeks, and then TDF monotherapy until week 240. We compared efficacy between the studies and safety in the pooled population at 240 weeks. Results At week 240, the proportion of patients with serum HBV DNA <15 IU/ml was not significantly different between the ETV and ADV resistance groups in the full analysis set (84.4% vs. 73.5%; p = 0.07), which was significantly different by on-treatment analysis (92.7% vs. 79.8%; p = 0.02). Virologic blips associated with poor medication adherence occurred in 7 patients throughout the 240 weeks. None developed additional HBV resistance mutations. Among the 170 HBV e antigen (HBeAg)-positive patients at baseline, 12 (7.1%) achieved HBeAg seroconversion at week 240. None achieved HBV surface antigen seroclearance. Significant decreases from baseline were observed at week 240 in the estimated glomerular filtration rate (−3.21 ml/min/1.73 m2 by the CKD-EPI equation, p <0.001) and bone mineral density (g/cm2) at the femur (−2.48%, p <0.001). Conclusions Up to 240 weeks of TDF monotherapy provided an increasing virologic response rate in heavily pretreated patients with HBV resistant to ETV and/or ADV. However, it was associated with poor serological responses and decreasing renal function and bone mineral density. (ClinicalTrials.gov No, NCT01639066 and NCT01639092). Lay summary In patients chronically infected with hepatitis B virus resistant to multiple drugs including lamivudine, entecavir, and/or adefovir, tenofovir disoproxil fumarate (TDF) monotherapy showed non-inferior efficacy compared with the combination therapy of TDF plus entecavir. Nonetheless, short-term TDF monotherapy was associated with suboptimal virologic response, and its long-term safety was uncertain. This study displayed that 240 weeks of TDF monotherapy provided a virologic response in most of those patients, but it was associated with poor serological responses and decreasing renal function and bone mineral density. Tenofovir disoproxil fumarate (TDF) monotherapy has displayed non-inferior efficacy to TDF plus entecavir (ETV) combination therapy in patients with hepatitis B virus (HBV) resistant to ETV and/or adefovir (ADV). Nonetheless, the virologic response rate was suboptimal in patients receiving up to 144 weeks of TDF monotherapy. We aimed to assess the efficacy and safety of TDF monotherapy given for up to 240 weeks. One trial enrolled patients with ETV resistance without ADV resistance (n = 90), and another trial included patients with ADV resistance (n = 102). Most patients (91.2%) also had lamivudine resistance. Patients were randomized 1:1 to receive TDF monotherapy or TDF + ETV combination therapy for 48 weeks, and then TDF monotherapy until week 240. We compared efficacy between the studies and safety in the pooled population at 240 weeks. At week 240, the proportion of patients with serum HBV DNA <15 IU/ml was not significantly different between the ETV and ADV resistance groups in the full analysis set (84.4% vs. 73.5%; p = 0.07), which was significantly different by on-treatment analysis (92.7% vs. 79.8%; p = 0.02). Virologic blips associated with poor medication adherence occurred in 7 patients throughout the 240 weeks. None developed additional HBV resistance mutations. Among the 170 HBV e antigen (HBeAg)-positive patients at baseline, 12 (7.1%) achieved HBeAg seroconversion at week 240. None achieved HBV surface antigen seroclearance. Significant decreases from baseline were observed at week 240 in the estimated glomerular filtration rate (−3.21 ml/min/1.73 m2 by the CKD-EPI equation, p <0.001) and bone mineral density (g/cm2) at the femur (−2.48%, p <0.001). Up to 240 weeks of TDF monotherapy provided an increasing virologic response rate in heavily pretreated patients with HBV resistant to ETV and/or ADV. However, it was associated with poor serological responses and decreasing renal function and bone mineral density.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
妖孽宇发布了新的文献求助10
1秒前
aa完成签到,获得积分20
1秒前
aaaa完成签到,获得积分10
1秒前
马香芦完成签到,获得积分10
2秒前
西红柿完成签到,获得积分10
3秒前
4秒前
懵懂的冬灵完成签到,获得积分10
4秒前
碧蓝可仁完成签到 ,获得积分10
5秒前
王拉拉完成签到 ,获得积分10
5秒前
西西完成签到,获得积分10
5秒前
深情安青应助mkmimii采纳,获得10
6秒前
上官若男应助小王采纳,获得10
6秒前
bkagyin应助旦皋采纳,获得10
6秒前
Orange应助欣欣采纳,获得10
7秒前
玄学大哥完成签到,获得积分10
7秒前
7秒前
7秒前
kk完成签到,获得积分10
7秒前
ww007完成签到,获得积分10
9秒前
科研通AI5应助hahaha123213123采纳,获得10
9秒前
misstwo完成签到,获得积分10
10秒前
研友_ZzrwqZ发布了新的文献求助10
10秒前
JY'完成签到,获得积分10
11秒前
一只小鲨鱼完成签到,获得积分10
12秒前
漂亮的哈密瓜完成签到,获得积分10
12秒前
量子星尘发布了新的文献求助10
12秒前
13秒前
LL发布了新的文献求助10
13秒前
苏苏完成签到,获得积分10
14秒前
14秒前
fabc5653219完成签到,获得积分10
15秒前
hkunyu完成签到 ,获得积分10
15秒前
jiao完成签到,获得积分10
16秒前
16秒前
LIUYONG完成签到,获得积分10
17秒前
ChatGPT发布了新的文献求助10
18秒前
18秒前
小王发布了新的文献求助10
18秒前
这个大头张呀完成签到,获得积分10
18秒前
19秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038388
求助须知:如何正确求助?哪些是违规求助? 3576106
关于积分的说明 11374447
捐赠科研通 3305798
什么是DOI,文献DOI怎么找? 1819322
邀请新用户注册赠送积分活动 892672
科研通“疑难数据库(出版商)”最低求助积分说明 815029