Evidence map›Paper›PMID 37129258›Full record

ArticleThe Journal of infectious diseases2023

Hepatitis B e Antigen-Negative Single Hepatocyte Analysis Shows Transcriptional Silencing and Slow Decay of Infected Cells With Treatment.

Chloe L Thio, Maraake Taddese, Yasmeen Saad, Kristina Zambo, Ruy M Ribeiro, Tanner Grudda, Mark S Sulkowski, Richard K Sterling, Yang Zhang, Eric D Young and 2 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Chloe L ThioDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-8851-8319
Maraake TaddeseDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yasmeen SaadDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kristina ZamboDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ruy M RibeiroLos Alamos National Laboratory, Los Alamos, New Mexico, USA.
Tanner GruddaDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MarylandUSA.
Mark S SulkowskiDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Richard K SterlingDivison of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA.
Yang ZhangDivision of Gastrointestinal and Hepatic Pathology, Joint Pathology Center, Silver Spring, Maryland, USA.
Eric D YoungDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hyon S HwangDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ashwin BalagopalDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Johns Hopkins University · USLos Alamos National Laboratory · USVirginia Commonwealth University · US

Funding

Spatial Models of Intrahepatic Hepatitis C Virus Propagation in HumansR01AI116868 · NIAID · TRIAD NATIONAL SECURITY, LLC · PI ASHWIN BALAGOPAL, Ruy M Ribeiro · 2016 to 2026
$8.5M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
HBV HIV Coinfection Research NetworkR01DK094818 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI STERLING, RICHARD K. · 2013 to 2017
$3.5M
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
Opportunities for Pathology Trainees in Cancer ResearchT32CA193145 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANDERS, ROBERT A., EBERHART, CHARLES G · 2015 to 2025
$2.6M
Patient Oriented Research in Hepatitis C-infected Injection Drug UsersK24DA034621 · NIDA · JOHNS HOPKINS UNIVERSITY · PI SULKOWSKI, MARK SEBASTIAN · 2012 to 2022
$1.2M
NCI NIH HHS T32 CA193145NIAID NIH HHS R01 AI116868NIAID NIH HHS R01 AI138810NIDA NIH HHS K24 DA034621NIDDK NIH HHS R01 DK094818NIH HHS R01 OD011095
6 · The paper itself

Abstract

backgroundNucleos(t)ide analogues (NUCs) rarely cure chronic hepatitis B (CHB) because they do not eliminate covalently closed circular deoxyribonucleic acid, the stable replication template. In hepatitis B e antigen (HBeAg)-positive CHB during NUCs, HBV-infected cells decline slowly and are transcriptionally silenced. Whether these occur in HBeAg-negative CHB is unknown.

methodsUsing paired liver biopsies separated by 2.7-3.7 years in 4 males with HIV and HBeAg-negative CHB at both biopsies and 1 male with HIV who underwent HBeAg seroconversion between biopsies, we quantified amounts of viral nucleic acids in hundreds of individual hepatocytes.

resultsIn the 4 persistently HBeAg-negative participants, HBV-infected hepatocytes ranged from 6.2% to 17.7% (biopsy 1) and significantly declined in 3 of 4 by biopsy 2. In the HBeAg seroconverter, the proportion was 97.4% (biopsy 1) and declined to 81.9% at biopsy 2 (P < .05). We extrapolated that HBV eradication with NUCs would take >100 years. At biopsy 1 in the persistently HBeAg-negative participants, 23%-56.8% of infected hepatocytes were transcriptionally inactive-higher than we observed in HBeAg-positive CHB-and significantly declined in 1 of 4 at biopsy 2.

conclusionsIn HBeAg-negative CHB on NUCs, the negligible decline in infected hepatocytes is similar to HBeAg-positive CHB, supporting the need for more potent therapeutics to achieve functional cure.

Indexed as

Hepatitis B, ChronicHIV InfectionsAntiviral AgentsDNA, ViralHepatitis B e AntigensHepatitis B virusHepatocytesHumansMaleAntiviral AgentsDNA, ViralHepatitis B e AntigenscccDNAddPCRHBeAg negativeHBV decayHBV transcription

Identifiers

PMID37129258
PMCPMC10629706
OpenAlexW4367668678

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.