A multicenter randomized-controlled trial of nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B

医学 中止 慢性肝炎 临床终点 HBeAg 乙型肝炎 随机对照试验 内科学 胃肠病学 不利影响 多中心试验 外科 多中心研究 免疫学 乙型肝炎病毒 病毒 乙型肝炎表面抗原
作者
Florian van Bömmel,Kerstin Stein,R Heyne,Jörg Petersen,Peter Buggisch,Christoph Berg,Stefan Zeuzem,Andreas Stallmach,Martin F. Sprinzl,Eckart Schott,A. Pathil-Warth,Ulrike von Arnim,Verena Keitel,Jürgen Lohmeyer,Karl‐Georg Simon,Christian Trautwein,Andreas Trein,D Hüppe,Markus Cornberg,Frank Lammert
出处
期刊:Journal of Hepatology [Elsevier BV]
卷期号:78 (5): 926-936 被引量:47
标识
DOI:10.1016/j.jhep.2022.12.018
摘要

•Stopping long-term NUC treatment can induce functional cure in HBeAg-negative patients.•Functional cure is associated with HBsAg levels <1,000 IU/ml at the time point of NUC treatment cessation.•All patients showed relapses in HBV DNA levels after NUC treatment discontinuation. But re-treatment with NUCs was only required in 14% of patients over a 96-week follow-up and no patient suffered hepatic decompensation. Background & AimsNucleos(t)ide analogues (NUCs) are the standard and mostly lifelong treatment for chronic HBeAg-negative hepatitis B, as functional cure (loss of HBsAg) is rarely achieved. Discontinuation of NUC treatment may lead to functional cure; however, to date, the evidence for this has been based on small or non-randomized clinical trials. The STOP-NUC trial was designed with the aim of increasing the HBsAg loss rate using a NUC treatment interruption approach.MethodsIn this multicenter, randomized-controlled trial, 166 HBeAg-negative patients with chronic hepatitis B on continuous long-term NUC treatment, with HBV DNA <172 IU/ml (1,000 copies/ml) for ≥4 years, were randomized to either stop (Arm A) or continue NUC treatment (Arm B) for a 96-week observation period. In total, 158 patients were available for final analysis, 79 per arm. The primary endpoint was sustained HBsAg loss up to week 96.ResultsOur study met its primary objective by demonstrating HBsAg loss in eight patients (10.1%, 95% CI 4.8%–19.5%) in Arm A and in no patient in Arm B (p = 0.006). Among patients with baseline HBsAg levels <1,000 IU/ml, seven (28%) achieved HBsAg loss. In Arm A, re-therapy was initiated in 11 (13.9%) patients, whereas 32 (40.5%) patients achieved sustained remission. A decrease of HBsAg >1 log IU/ml was observed in 16 patients (20.3%) in Arm A and in one patient (1.3%) in Arm B. No serious adverse events related to treatment cessation occurred.ConclusionsCessation of NUC treatment was associated with a significantly higher rate of HBsAg loss than continued NUC treatment, which was largely restricted to patients with end of treatment HBsAg levels <1,000 IU/ml.Impact and implicationsAs HBeAg-negative patients with chronic hepatitis B on nucleos(t)ide analogues (NUCs) rarely achieve functional cure, treatment is almost always lifelong. The STOP-NUC trial was conducted to investigate whether discontinuing long-term NUC treatment can increase the cure rate. We found that some patients achieved functional cure after stopping NUCs, which was especially pronounced in patients with HBsAg levels <1,000 at the end of NUC treatment, and that many did not need to resume therapy. The results of the Stop-NUC trial provide evidence for the concept of stopping NUC treatment as a therapeutic option that can induce functional cure. Nucleos(t)ide analogues (NUCs) are the standard and mostly lifelong treatment for chronic HBeAg-negative hepatitis B, as functional cure (loss of HBsAg) is rarely achieved. Discontinuation of NUC treatment may lead to functional cure; however, to date, the evidence for this has been based on small or non-randomized clinical trials. The STOP-NUC trial was designed with the aim of increasing the HBsAg loss rate using a NUC treatment interruption approach. In this multicenter, randomized-controlled trial, 166 HBeAg-negative patients with chronic hepatitis B on continuous long-term NUC treatment, with HBV DNA <172 IU/ml (1,000 copies/ml) for ≥4 years, were randomized to either stop (Arm A) or continue NUC treatment (Arm B) for a 96-week observation period. In total, 158 patients were available for final analysis, 79 per arm. The primary endpoint was sustained HBsAg loss up to week 96. Our study met its primary objective by demonstrating HBsAg loss in eight patients (10.1%, 95% CI 4.8%–19.5%) in Arm A and in no patient in Arm B (p = 0.006). Among patients with baseline HBsAg levels <1,000 IU/ml, seven (28%) achieved HBsAg loss. In Arm A, re-therapy was initiated in 11 (13.9%) patients, whereas 32 (40.5%) patients achieved sustained remission. A decrease of HBsAg >1 log IU/ml was observed in 16 patients (20.3%) in Arm A and in one patient (1.3%) in Arm B. No serious adverse events related to treatment cessation occurred. Cessation of NUC treatment was associated with a significantly higher rate of HBsAg loss than continued NUC treatment, which was largely restricted to patients with end of treatment HBsAg levels <1,000 IU/ml.
最长约 10秒,即可获得该文献文件

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
帅气的宽完成签到 ,获得积分10
1秒前
小丸子完成签到 ,获得积分10
3秒前
634301059完成签到 ,获得积分10
12秒前
George完成签到,获得积分10
14秒前
科研通AI2S应助科研通管家采纳,获得10
17秒前
打打应助科研通管家采纳,获得10
17秒前
科研通AI2S应助科研通管家采纳,获得10
17秒前
七月完成签到,获得积分10
20秒前
22秒前
路路完成签到 ,获得积分10
23秒前
单薄念波发布了新的文献求助10
26秒前
ymr完成签到 ,获得积分10
29秒前
hellomoon完成签到 ,获得积分10
31秒前
如意的馒头完成签到 ,获得积分10
31秒前
单薄念波完成签到,获得积分10
36秒前
czj完成签到 ,获得积分10
37秒前
海盗船长完成签到,获得积分10
44秒前
45秒前
amai完成签到,获得积分10
46秒前
wenhuanwenxian完成签到 ,获得积分10
47秒前
渠建武发布了新的文献求助10
52秒前
提莫silence完成签到 ,获得积分10
53秒前
小小完成签到 ,获得积分10
57秒前
ycd完成签到,获得积分10
59秒前
橘子海完成签到 ,获得积分10
59秒前
研友完成签到 ,获得积分10
1分钟前
辣目童子完成签到 ,获得积分10
1分钟前
小蘑菇应助Jialing采纳,获得10
1分钟前
谨慎鹏涛完成签到 ,获得积分10
1分钟前
Star完成签到,获得积分10
1分钟前
白昼の月完成签到 ,获得积分0
1分钟前
快递乱跑完成签到 ,获得积分10
1分钟前
不知道完成签到,获得积分10
1分钟前
Lz555完成签到 ,获得积分10
1分钟前
1分钟前
背后海亦发布了新的文献求助10
1分钟前
三木完成签到 ,获得积分10
1分钟前
无私翎完成签到 ,获得积分10
1分钟前
一勺四季完成签到 ,获得积分10
1分钟前
香菜大王完成签到 ,获得积分10
1分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 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 3968559
求助须知:如何正确求助?哪些是违规求助? 3513358
关于积分的说明 11167340
捐赠科研通 3248714
什么是DOI,文献DOI怎么找? 1794453
邀请新用户注册赠送积分活动 875065
科研通“疑难数据库(出版商)”最低求助积分说明 804664