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

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.

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Publication Details

Journal
PLoS Computational Biology
Published
2025-01-09
DOI
https://doi.org/10.1371/journal.pcbi.1012615
Citations
1
Primary Topic
Hepatitis B Virus Studies
Type
article
Field-Weighted Citation Impact
1.35

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article

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

Hyeongki Park, Maura Dandri, Lena Allweiss, Yasuhito Tanaka et al.
1 citations
PLoS Computational Biology
Hepatitis B Virus Studies
1.35
article

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

Hyeongki Park, Maura Dandri, Lena Allweiss, Yasuhito Tanaka, Takaji Wakita, Naotoshi Nakamura, Kosaku Kitagawa, Eiryo Kawakami, Kazuyuki Aihara, Takara Nishiyama, Shinji Nakaoka, Sanae Hayashi, Masamichi Muramatsu, Shingo Iwami, Alan S. Perelson, Koichi Watashi, Natthaya Chuaypen, Masanori Atsukawa, Senko Tsukuda, Pisit Tangkijvanich, Kentaro Matsuura, Takeshi Matsui, Yasuhisa Fujita, Masashi Iwamoto, Kwang Su Kim
article en
1 citations

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.

PLoS Computational BiologyVol. 21(1)
Los Alamos National Laboratory (US), Kyushu University (JP), Chulalongkorn University (TH), Universität Hamburg (DE), Chiba University (JP), Tokyo University of Science (JP), Hokkaido University (JP), Kyoto University (JP), Nagoya City University (JP), University of Oxford (GB), National Institute of Infectious Diseases (JP), Institute of Mathematics and Informatics (BG), University Medical Center Hamburg-Eppendorf (DE), RIKEN (JP), German Center for Infection Research (DE), Czech Academy of Sciences, Institute of Mathematics (CZ), Science Groove (Japan) (JP), Teine Keijinkai Hospital (JP), RIKEN Center for Integrative Medical Sciences (JP), Japanese Foundation For Cancer Research (JP), Nagoya University (JP), The University of Tokyo (JP), Nippon Medical School (JP), Pukyong National University (KR), Kumamoto University (JP)
U.S. Department of Energy, Takeda Science Foundation, Japan Agency for Medical Research and Development, Taiju Life Social Welfare Foundation, Ministry of Education, Culture, Sports, Science and Technology, National Research Foundation of Korea, Japan Prize Foundation, Secom Science and Technology Foundation, Smoking Research Foundation, National Institutes of Health, National Nuclear Security Administration, Japan Society for the Promotion of Science, JST-Mirai Program, Moonshot Research and Development Program, Los Alamos National Laboratory
Good health and well-being
Openalex Percentile: Top 24%
Hepatitis B Virus Studies
1.35
DOIOpen Access PDFOpenAlex
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