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
糖宝完成签到 ,获得积分10
2秒前
KX2024完成签到,获得积分10
5秒前
松松发布了新的文献求助20
8秒前
nusiew完成签到,获得积分10
8秒前
huiluowork完成签到 ,获得积分10
9秒前
陶醉的翠霜完成签到 ,获得积分10
9秒前
9秒前
冷静如松完成签到 ,获得积分10
16秒前
18秒前
浮云完成签到 ,获得积分10
19秒前
屈岂愈完成签到,获得积分10
20秒前
34秒前
Pupil完成签到,获得积分10
34秒前
偏偏意气用事完成签到,获得积分10
35秒前
安安完成签到,获得积分10
39秒前
cttc完成签到,获得积分10
40秒前
Chnimike完成签到 ,获得积分10
40秒前
44秒前
红茸茸羊完成签到 ,获得积分10
44秒前
年轻千愁完成签到 ,获得积分10
46秒前
liu完成签到,获得积分10
47秒前
量子星尘发布了新的文献求助10
47秒前
Wanyeweiyu完成签到,获得积分10
49秒前
Fury完成签到 ,获得积分10
54秒前
风中幻梦完成签到,获得积分10
56秒前
bigpluto完成签到,获得积分10
57秒前
59秒前
是谁还没睡完成签到 ,获得积分10
1分钟前
盘尼西林发布了新的文献求助10
1分钟前
zzz完成签到 ,获得积分10
1分钟前
dktrrrr完成签到,获得积分10
1分钟前
科研通AI2S应助科研通管家采纳,获得10
1分钟前
丘比特应助科研通管家采纳,获得20
1分钟前
1分钟前
ccc完成签到,获得积分10
1分钟前
萧秋灵完成签到,获得积分10
1分钟前
缓慢冥幽完成签到,获得积分10
1分钟前
旺仔同学完成签到,获得积分10
1分钟前
吉以寒完成签到,获得积分10
1分钟前
科研老兵完成签到,获得积分10
1分钟前
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
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
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 4038066
求助须知:如何正确求助?哪些是违规求助? 3575779
关于积分的说明 11373801
捐赠科研通 3305584
什么是DOI,文献DOI怎么找? 1819239
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022