Nucleos(t)ide withdrawal versus nucleos(t)ide withdrawal with adjuvant pegylated-interferon in HBeAg-negative hepatitis B virus infection (NUC-B trial)
File(s)
Published version (onlline)
Author(s)
Type
Journal Article
Abstract
Background:
Finite therapy resulting in sustained hepatitis B surface antigen (HBsAg) loss for patients with chronic HBV infection (CHB) is an important therapeutic goal. In patients with HBeAg-negative infection, nucleos(t)ide analog (NA) withdrawal may achieve HBsAg loss in 5%–20% of patients after 3 years. Pegylated interferon (PEG-IFNα) is a recognized treatment for CHB.
Methods:
NUC-B was a randomized, multicenter trial in NA-treated non-cirrhotic HBeAg-negative patients with CHB. Patients were allocated to either NA withdrawal alone (control) or NA withdrawal followed by a 16-week course of PEG-IFNα 180 μg weekly commencing 4 weeks after NA cessation (PEG-IFNα). The primary endpoint was HBsAg loss at 3 years.
Results:
The target recruitment of 240 patients was not achieved. In all, 156 patients, 82 to the control arm, 74 to the PEG-IFNα arm, were recruited between 2017 and 2021; median age 45 years, 24% female, HBV genotypes—A 16%, B 6%, C 4%, D 24%, E 22%, other 1%, ānd unknown 26%. At 3 years, 3% of patients in the control arm and 14% of patients in the PEG-IFNα arm lost HBsAg (OR 5.39; 95% CI (1.11, 26.19); p=0.037). In the control arm, 34.9% of patients returned to NA therapy compared with 28.4% in the PEG-IFNα arm. Exaggerated flares occurred in 27.9% of patients in the control arm compared with 13.4% in the PEG-IFNα arm.
Conclusions:
The use of adjuvant PEG-IFNα therapy after withdrawal of NA therapy increases the rate of HBsAg loss while simultaneously reducing the number of exaggerated flares.
Finite therapy resulting in sustained hepatitis B surface antigen (HBsAg) loss for patients with chronic HBV infection (CHB) is an important therapeutic goal. In patients with HBeAg-negative infection, nucleos(t)ide analog (NA) withdrawal may achieve HBsAg loss in 5%–20% of patients after 3 years. Pegylated interferon (PEG-IFNα) is a recognized treatment for CHB.
Methods:
NUC-B was a randomized, multicenter trial in NA-treated non-cirrhotic HBeAg-negative patients with CHB. Patients were allocated to either NA withdrawal alone (control) or NA withdrawal followed by a 16-week course of PEG-IFNα 180 μg weekly commencing 4 weeks after NA cessation (PEG-IFNα). The primary endpoint was HBsAg loss at 3 years.
Results:
The target recruitment of 240 patients was not achieved. In all, 156 patients, 82 to the control arm, 74 to the PEG-IFNα arm, were recruited between 2017 and 2021; median age 45 years, 24% female, HBV genotypes—A 16%, B 6%, C 4%, D 24%, E 22%, other 1%, ānd unknown 26%. At 3 years, 3% of patients in the control arm and 14% of patients in the PEG-IFNα arm lost HBsAg (OR 5.39; 95% CI (1.11, 26.19); p=0.037). In the control arm, 34.9% of patients returned to NA therapy compared with 28.4% in the PEG-IFNα arm. Exaggerated flares occurred in 27.9% of patients in the control arm compared with 13.4% in the PEG-IFNα arm.
Conclusions:
The use of adjuvant PEG-IFNα therapy after withdrawal of NA therapy increases the rate of HBsAg loss while simultaneously reducing the number of exaggerated flares.
Date Issued
2026-08-04
Date Acceptance
2026-06-12
Citation
Hepatology, 2026
ISSN
0270-9139
Publisher
Ovid Technologies (Wolters Kluwer Health)
Journal / Book Title
Hepatology
Copyright Statement
Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, LLC. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/42549812
PII: 01515467-990000000-01643
Subjects
Hepatitis B Surface Antigen
clinical remission
exaggerated flare
immunomodulator
randomized controlled trial
Publication Status
Published online
Coverage Spatial
United States
Date Publish Online
2026-08-04