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

Authors :
van Bömmel F
Stein K
Heyne R
Petersen J
Buggisch P
Berg C
Zeuzem S
Stallmach A
Sprinzl M
Schott E
Pathil-Warth A
von Arnim U
Keitel V
Lohmeyer J
Simon KG
Trautwein C
Trein A
Hüppe D
Cornberg M
Lammert F
Ingiliz P
Zachoval R
Hinrichsen H
Zipprich A
Klinker H
Schulze Zur Wiesch J
Schmiedeknecht A
Brosteanu O
Berg T
Source :
Journal of hepatology [J Hepatol] 2023 May; Vol. 78 (5), pp. 926-936. Date of Electronic Publication: 2023 Mar 28.
Publication Year :
2023

Abstract

Background & Aims: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusions: 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.<br />Impact and Implications: 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.<br /> (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1600-0641
Volume :
78
Issue :
5
Database :
MEDLINE
Journal :
Journal of hepatology
Publication Type :
Academic Journal
Accession number :
37062574
Full Text :
https://doi.org/10.1016/j.jhep.2022.12.018