目的:Nucleos(t)ide类似物(NUCs)是慢性HBeAg阴性乙型肝炎的标准和大多数终身治疗,作为功能治愈(HBsAg的损失)很少实现。停止NUC治疗可能导致功能性治愈;然而,到目前为止,这方面的证据是基于小型或非随机临床试验.STOP-NUC试验旨在使用NUC治疗中断方法增加HBsAg损失率。
方法:在这个多中心中,随机对照试验,166例HBeAg阴性慢性乙型肝炎患者接受持续长期NUC治疗,HBVDNA<172IU/ml(1,000拷贝/ml)≥4年,随机分为停止(A组)或继续进行NUC治疗(B组),为期96周。总的来说,158名患者可用于最终分析,每臂79。主要终点是持续的HBsAg消失,直到第96周。
结果:我们的研究通过证明8例患者的HBsAg消失(10.1%,A组95%CI4.8%-19.5%),B组无患者(p=0.006)。在基线HBsAg水平<1,000IU/ml的患者中,七(28%)实现HBsAg消失。在A组中,11例(13.9%)患者开始重新治疗,而32例(40.5%)患者获得持续缓解。在A组中的16例患者(20.3%)和B组中的一名患者(1.3%)中观察到HBsAg>1logIU/ml的降低。没有发生与治疗停止有关的严重不良事件。
结论:停止NUC治疗与HBsAg消失率明显高于持续NUC治疗相关,这在很大程度上限于治疗结束时HBsAg水平<1,000IU/ml的患者。
■作为HBeAg阴性慢性乙型肝炎患者的核苷(酸)类似物(NUCs)很少实现功能治愈,治疗几乎总是终身的。进行了STOP-NUC试验,以调查停止长期NUC治疗是否可以提高治愈率。我们发现一些患者在停止NUCs后实现了功能治愈,在NUC治疗结束时,HBsAg水平<1,000的患者尤其明显,许多人不需要恢复治疗。Stop-NUC试验的结果为停止NUC治疗作为一种可以诱导功能性治愈的治疗选择的概念提供了证据。
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.
As 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.