Evidence map›Paper›PMID 33004689›Full record

ArticleJCI insight2020

Single hepatocytes show persistence and transcriptional inactivity of hepatitis B.

Ashwin Balagopal, Tanner Grudda, Ruy M Ribeiro, Yasmeen S Saad, Hyon S Hwang, Jeffrey Quinn, Michael Murphy, Kathleen Ward, Richard K Sterling, Yang Zhang and 4 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
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  18. Evaluation of the HBV liver reservoir with fine needle aspirates.JHEP reports : innovation in hepatology · 2023
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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

14 authors at 4 institutions in 2 countries.

Ashwin BalagopalDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Tanner GruddaDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ruy M RibeiroTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Yasmeen S SaadDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hyon S HwangDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jeffrey QuinnDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Michael MurphyDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kathleen WardDepartment 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.
Yang ZhangDepartment of Pathology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Alan S PerelsonTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Mark S SulkowskiDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
William O OsburnDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Chloe L ThioDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Johns Hopkins University · USLos Alamos National Laboratory · USJohns Hopkins Hospital · 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
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
NIAID NIH HHS R01 AI116269NIAID NIH HHS R01 AI116868NIAID NIH HHS R01 AI138810NIDA NIH HHS K24 DA034621NIDDK NIH HHS R01 DK094818NIH HHS R01 OD011095
6 · The paper itself

Abstract

There is no cure for the more than 270 million people chronically infected with HBV. Nucleos(t)ide analogs (NUCs), the mainstay of anti-HBV treatment, block HBV reverse transcription. NUCs do not eliminate the intranuclear covalently closed circular DNA (cccDNA), from which viral RNAs, including pregenomic RNA (pgRNA), are transcribed. A key gap in designing a cure is understanding how NUCs affect HBV replication and transcription because serum markers yield an incomplete view of intrahepatic HBV. We applied single-cell laser capture microdissection and droplet digital PCR to paired liver biopsies collected from 5 HBV/HIV-coinfected persons who took NUCs over 2-4 years. From biopsy 1 to 2, proportions of HBV-infected hepatocytes declined with adherence to NUC treatment (P < 0.05); we extrapolated that eradication of HBV will take over 10 decades with NUCs in these participants. In individual hepatocytes, pgRNA levels diminished 28- to 73-fold during NUC treatment, corresponding with decreased tissue HBV core antigen staining (P < 0.01). In 4 out of 5 participants, hepatocytes with cccDNA but undetectable pgRNA (transcriptionally inactive) were present, and these were enriched in 3 participants during NUC treatment. Further work to unravel mechanisms of cccDNA transcriptional inactivation may lead to therapies that can achieve this in all hepatocytes, resulting in a functional cure.

Indexed as

AdultAntiviral AgentsDNA, CircularDNA, ViralHepatitis BHepatitis B Surface AntigensHepatitis B virusHepatocytesHumansLongitudinal StudiesMaleMiddle AgedUnited StatesVirus ReplicationAntiviral AgentsDNA, CircularDNA, ViralHepatitis B Surface AntigensHepatitisHepatologyInfectious diseaseMolecular biologyTranscription

Identifiers

PMID33004689
PMCPMC7566712
OpenAlexW3090556888

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.