Our research
Chronic hepatitis B virus (HBV) infection is characterized by persistent hepatic inflammation and immune activation.
Hepatocytes serve as the primary viral reservoir, and most individuals with chronic HBV infection do not achieve spontaneous cure. While some patients establish long-term immune control of the virus, others require antiviral treatment with nucleos(t)ide analogues (NAs).
A key unanswered question in HBV management is whether antiviral treatment can safely be discontinued in selected patients or whether lifelong therapy is required.
Projects
We have several ongoing projects.
Nuc-Stop - the Norwegian Nucleoside Analogue Stop Study
Nuc-Stop is a multicentre clinical study involving eleven study sites across Norway, Sweden, Denmark, and Ethiopia.
The study investigates whether discontinuation of long-term nucleos(t)ide analogue treatment in selected individuals with chronic HBV infection can trigger beneficial immune responses leading to sustained viral control and ultimately a functional cure.
The clinical phase of the study has been completed, and the primary results have been published. Ongoing work focuses on in-depth analyses of the unique biobank and clinical datasets generated through the project, with particular emphasis on immune signatures associated with treatment outcomes.
Read more at U.S. Library of Medicine - ClinicalTrials ID: NCT03681132.
Personalized treatment and care in chronic hepatitis B
This translational research project is based on the extensive biobank established through the Nuc-Stop study. The overall aim is to identify immunological biomarkers capable of predicting clinical outcomes following treatment discontinuation and to improve our understanding of the immune mechanisms driving chronic HBV infection.
The project is conducted in close collaboration with Karolinska Institutet, Sweden, and inludes several interdisciplinary and cross-sector partnerships. Through these activities, the project aims to contribute to more personalized HBV management, improved public health interventions, and future strategies for functional cure.
In collaboration with Caritas Norway, we work to increase awareness and knowledge of hepatitis B among migrant communities, an important population disproportionately affected by chronic HBV infection.
The project also includes collaboration with the biotechnology company Zimmer & Peacock to develop a point-of-care HBV DNA test that may improve access to monitoring and treatment in both high- and low- resource settings.
Selected publications
- A Distinct Immune Signature Characterizes Cirrhosis in Ethiopian Individuals With Chronic HBV Infection. MacLeod J, Gudissa FG, Jeylan A, Berhe N, Desalegn H, Rossvoll L, Johannessen A, Björkström NK, Reikvam DH, Niehrs A. Aliment Pharmacol Ther. 2026 Oct;64(7):951-964. doi: 10.1111/apt.70816. Epub 2026 Jul 1. PMID: 42387268 Free PMC article.
- Hepatic flares, their immune signatures, and ALT variability after nucleos(t)ide analogue cessation in HBeAg-negative hepatitis B. Holmberg M, Niehrs A, Dalgard O, Berhe N, Desalegn H, Aleman S, Weis N, Stenstad T, Heggelund L, Samuelsen E, Karlsen LN, Lindahl K, Kleppa E, Winckelmann AA, Brugger-Synnes P, Simonsen HE, Svendsen J, Björkström NK, Reikvam DH, Johannessen A. JHEP Rep. 2026 Jul;8(7):101875. doi: 10.1016/j.jhepr.2026.101875. Epub 2026 Apr 29. PMID: 42067192
- Oral Microbiome Diversity Matters on Nucleos(t)ide Analogue Cessation in Chronic Hepatitis B. Ghorbani M, Kvedaraite A, Al-Manei K, Too CB, Cederberg S, Johannessen A, Reikvam DH, Valentini D, Maucourant C, Björkström NK, Aleman S, Sällberg Chen M.J Infect Dis. 2025 Dec 2:jiaf591. doi: 10.1093/infdis/jiaf591. Online ahead of print. PMID: 41328917
- Clinical trial: An open-label, randomised trial of different re-start strategies after treatment withdrawal in HBeAg negative chronic hepatitis B. Johannessen A, Reikvam DH, Aleman S, Berhe N, Weis N, Desalegn H, Stenstad T, Heggelund L, Samuelsen E, Karlsen LN, Lindahl K, Pettersen FO, Iversen J, Kleppa E, Bollerup S, Winckelmann AA, Brugger-Synnes P, Simonsen HE, Svendsen J, Kran AB, Holmberg M, Olsen IC, Rueegg CS, Dalgard O.Aliment Pharmacol Ther. 2024 Aug;60(4):434-445. doi: 10.1111/apt.18147. Epub 2024 Jul 5.PMID: 38970293
- Treatment cessation in HBeAg-negative chronic hepatitis B: clinical response is associated with increase in specific proinflammatory cytokines. Holmberg M, Aass HCD, Dalgard O, Samuelsen E, Sun D, Björkström NK, Johannessen A, Reikvam DH.Sci Rep. 2023 Dec 18;13(1):22590. doi: 10.1038/s41598-023-50216-y.PMID: 38114718
- Systematic review and individual-patient-data meta-analysis of non-invasive fibrosis markers for chronic hepatitis B in Africa. Johannessen A et al, Nat Commun. 2023 Jan 3;14(1):45. doi: 10.1038/s41467-022-35729-w.
