Evidence map›Paper›PMID 39787253›Full record

ArticlePLoS computational biology2025

Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers.

Kwang Su Kim, Masashi Iwamoto, Kosaku Kitagawa, Hyeongki Park, Sanae Hayashi, Senko Tsukuda, Takeshi Matsui, Masanori Atsukawa, Kentaro Matsuura, Natthaya Chuaypen and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS computational biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

25 authors.

Kwang Su Kiminterdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan.
Masashi Iwamotointerdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan.
Kosaku Kitagawainterdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan.
Hyeongki Parkinterdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan.
Sanae HayashiDepartment of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Senko TsukudaNuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Takeshi MatsuiCenter for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.ORCID 0000-0003-4740-1824
Masanori AtsukawaDepartment of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan.
Kentaro MatsuuraDepartment of Gastroenterology and Metabolism, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
Natthaya ChuaypenCenter of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Pisit TangkijvanichCenter of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Lena AllweissDepartment of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Takara Nishiyamainterdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan.
Naotoshi Nakamurainterdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan.ORCID 0000-0002-4798-3660
Yasuhisa Fujitainterdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan.
Eiryo KawakamiArtificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Shinji NakaokaFaculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
Masamichi MuramatsuDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Kazuyuki AiharaInternational Research Center for Neurointelligence, The University of Tokyo Institutes for Advanced Study, The University of Tokyo, Tokyo, Japan.
Takaji WakitaDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Alan S PerelsonTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.ORCID 0000-0002-2455-0002
Maura DandriCenter of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Koichi WatashiDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.ORCID 0000-0002-4536-9966
Shingo Iwamiinterdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan.ORCID 0000-0002-1780-350X
Yasuhito TanakaDepartment of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID 0000-0002-2473-6966

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
Collaborative Integration of HCV Molecular Virology and Mathematical ModelingR01AI078881 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PERELSON, ALAN S, UPRICHARD, SUSAN L. · 2011 to 2025
$7.5M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
NIAID NIH HHS R01 AI078881NIAID NIH HHS R01 AI116868NIH HHS R01 OD011095
6 · The paper itself

Abstract

Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination of hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as a liver biopsy, which makes it impractical to access the dynamics of cccDNA in patients. Although HBV RNA and HBV core-related antigens (HBcrAg) have been proposed as surrogate markers for evaluating cccDNA activity, they do not necessarily estimate the amount of cccDNA. Here, we employed a recently developed multiscale mathematical model describing intra- and intercellular viral propagation and applied it in HBV-infected patients under treatment. We developed a model that can predict intracellular HBV dynamics by use of extracellular viral markers, including HBsAg, HBV DNA, and HBcrAg in peripheral blood. Importantly, the model prediction of the amount of cccDNA in patients over time was confirmed to be well correlated with the data for quantified cccDNA by paired liver biopsy. Thus, our method combining classic and emerging surrogate markers enables us to predict the decay dynamics of cccDNA in patients undergoing treatment.

Indexed as

DNA, CircularDNA, ViralHepatitis BHepatitis B virusBiomarkersComputational BiologyHepatitis B Core AntigensHepatitis B Surface AntigensHumansLiverModels, BiologicalBiomarkersDNA, CircularDNA, ViralHepatitis B Core AntigensHepatitis B Surface Antigens

Identifiers

PMID39787253
PMCPMC11753647

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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.