Evidence map›Paper›PMID 35797115›Full record

ArticleThe Journal of clinical investigation2022

Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment.

Tanner Grudda, Hyon S Hwang, Maraake Taddese, Jeffrey Quinn, Mark S Sulkowski, Richard K Sterling, Ashwin Balagopal, Chloe L Thio

Open access · goldAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
9.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 65 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. [Clinical significance and occurrence mechanism of hepatitis B virus DNA integration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. HBV Suppression by Nucleos(t)ide Analogues Reduces PD-1 Expression on Liver-Resident T Cells.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. [The concept of a fountional cure for hepatitis B keeps pace with the times].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Tanner GruddaDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Hyon S HwangDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Maraake TaddeseDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jeffrey QuinnDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mark S SulkowskiDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Richard K SterlingDivision of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA.
Ashwin BalagopalDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Chloe L ThioDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Johns Hopkins University · USVirginia Commonwealth University · US

Funding

HBV HIV Coinfection Research NetworkR01DK094818 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI STERLING, RICHARD K. · 2013 to 2017
$3.5M
Immune correlates of acute HBV recovery with and without HIVR01AI116269 · NIAID · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L, THIO, CHLOE L · 2015 to 2019
$3.2M
Characterization of silently HBV-infected hepatocytes in HIV co-infectionR01AI138810 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BALAGOPAL, ASHWIN, THIO, CHLOE L · 2018 to 2021
$3.2M
Patient Oriented Research in Hepatitis C-infected Injection Drug UsersK24DA034621 · NIDA · JOHNS HOPKINS UNIVERSITY · PI SULKOWSKI, MARK SEBASTIAN · 2012 to 2022
$1.2M
Mechanisms of HBV cccDNA transcriptional regulation in persons with and without HIVR56AI138810 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BALAGOPAL, ASHWIN, THIO, CHLOE L · 2023 to 2023
$811k
Unraveling sources of hepatitis B surface antigen before and after nucleos(t)ide analogue treatment in People with HIVR21AI157760 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BALAGOPAL, ASHWIN, THIO, CHLOE L · 2021 to 2022
$450k
Identifying the source of hepatitis B surface antigen in people with hepatitis B-HIV co-infectionR21AI165166 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BALAGOPAL, ASHWIN, THIO, CHLOE L · 2021 to 2022
$450k
NIAID NIH HHS R01 AI116269NIAID NIH HHS R01 AI138810NIAID NIH HHS R21 AI157760NIAID NIH HHS R21 AI165166NIAID NIH HHS R56 AI138810NIDA NIH HHS K24 DA034621NIDDK NIH HHS R01 DK094818
6 · The paper itself

Abstract

The focus of hepatitis B functional cure, defined as sustained loss of hepatitis B virus (HBV) surface antigen (HBsAg) and HBV DNA from blood, is on eliminating or silencing the intranuclear template for HBV replication, covalently closed circular DNA (cccDNA). However, HBsAg also derives from HBV DNA integrated into the host genome (iDNA). Little is known about the contribution of iDNA to circulating HBsAg with current therapeutics. We applied a multiplex droplet digital PCR assay to demonstrate that iDNA is responsible for maintaining HBsAg quantities in some individuals. Using paired bulk liver tissue from 16 HIV/HBV-coinfected persons on nucleos(t)ide analog (NUC) therapy, we demonstrate that people with larger HBsAg declines between biopsies derive HBsAg from cccDNA, whereas people with stable HBsAg levels derive predominantly from iDNA. We applied our assay to individual hepatocytes in paired tissues from 3 people and demonstrated that the individual with significant HBsAg decline had a commensurate loss of infected cells with transcriptionally active cccDNA, while individuals without HBsAg decline had stable or increasing numbers of cells producing HBsAg from iDNA. We demonstrate that while NUC therapy may be effective at controlling cccDNA replication and transcription, innovative treatments are required to address iDNA transcription that sustains HBsAg production.

Indexed as

Hepatitis BHepatitis B, ChronicAntigens, SurfaceAntiviral AgentsDNA, CircularDNA, ViralHepatitis B Surface AntigensHepatitis B virusHumansLiverAntigens, SurfaceAntiviral AgentsDNA, CircularDNA, ViralHepatitis B Surface AntigensAntigenHepatitisInfectious diseaseMolecular biologyVirology

Identifiers

PMID35797115
PMCPMC9473722
OpenAlexW4284680923

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.