Ubiquitous expression of HBsAg from integrated HBV DNA in patients with low viral load.


Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
10 2021
Historique:
received: 11 02 2021
revised: 21 04 2021
accepted: 27 04 2021
pubmed: 19 5 2021
medline: 8 2 2022
entrez: 18 5 2021
Statut: ppublish

Résumé

Loss of serum HBsAg is a hallmark of spontaneous and therapy induced resolution of HBV infection, since it generally reflects a profound decrease in viral replication. However, integrated HBV DNA can contribute to HBsAg expression independent of viral replication. The relative contributions of these sources of HBsAg are not well understood. Specifically, it is not known whether actively transcribed HBV integration could spread throughout the entire liver. The relative distribution of HBsAg and HBV RNA in liver biopsy tissue from HBeAg-negative (HBe Immunohistochemistry and ISH analysis revealed HBsAg and HBV RNA positivity in virtually all hepatocytes in the liver of some HBe Transcriptionally active HBV integration can extend to the entire liver in some HBe Loss of serum hepatitis B surface antigen (HBsAg) indicates resolution of HBV infection. However, integrated HBV DNA can contribute to HBsAg production independently of viral replication. We investigated the extent of HBsAg-producing viral integration in the livers of patients with low serum viral loads. Our findings suggest that transcriptionally active HBV integration can extend to the entire liver in some patients, questioning the clinical utility of HBsAg as a surrogate marker for viral replication.

Sections du résumé

BACKGROUND & AIMS
Loss of serum HBsAg is a hallmark of spontaneous and therapy induced resolution of HBV infection, since it generally reflects a profound decrease in viral replication. However, integrated HBV DNA can contribute to HBsAg expression independent of viral replication. The relative contributions of these sources of HBsAg are not well understood. Specifically, it is not known whether actively transcribed HBV integration could spread throughout the entire liver.
METHODS
The relative distribution of HBsAg and HBV RNA in liver biopsy tissue from HBeAg-negative (HBe
RESULTS
Immunohistochemistry and ISH analysis revealed HBsAg and HBV RNA positivity in virtually all hepatocytes in the liver of some HBe
CONCLUSIONS
Transcriptionally active HBV integration can extend to the entire liver in some HBe
LAY SUMMARY
Loss of serum hepatitis B surface antigen (HBsAg) indicates resolution of HBV infection. However, integrated HBV DNA can contribute to HBsAg production independently of viral replication. We investigated the extent of HBsAg-producing viral integration in the livers of patients with low serum viral loads. Our findings suggest that transcriptionally active HBV integration can extend to the entire liver in some patients, questioning the clinical utility of HBsAg as a surrogate marker for viral replication.

Identifiants

pubmed: 34004216
pii: S0168-8278(21)00328-7
doi: 10.1016/j.jhep.2021.04.051
pii:
doi:

Substances chimiques

DNA, Viral 0
Hepatitis B Antibodies 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

840-847

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare no conflict of interest.

Auteurs

Marie-Anne Meier (MA)

Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland; Institute of Pathology, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland.

Diego Calabrese (D)

Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland.

Aleksei Suslov (A)

Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland.

Luigi M Terracciano (LM)

Division of Gastroenterology and Hepatology, University Hospital Basel, Basel CH-4031, Switzerland.

Markus H Heim (MH)

Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland; Institute of Pathology, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland. Electronic address: markus.heim@unibas.ch.

Stefan Wieland (S)

Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland. Electronic address: stefan.wieland@unibas.ch.

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Classifications MeSH