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

Journal Article · Wed Jan 08 23:00:00 EST 2025 · PLoS Computational Biology (Online)

DOI:https://doi.org/10.1371/journal.pcbi.1012615· OSTI ID:2556828

Kim, Kwang Su ^[1]; Iwamoto, Masashi ^[2]; Kitagawa, Kosaku ^[3]; Hayashi, Sanae ^[4]; Tsukuda, Senko ^[5]; Matsui, Takeshi ^[6]; Atsukawa, Masanori ^[7]; Chuaypen, Natthaya ^[8]; Tangkijvanich, Pisit ^[8]; Allweiss, Lena ^[9]; Nishiyama, Takara ^[3]; Nakamura, Naotoshi ^[3]; Fujita, Yasuhisa ^[3]; Kawakami, Eiryo ^[10]; Nakaoka, Shinji ^[11]; Muramatsu, Masamichi ^[12]; Aihara, Kazuyuki ^[13]; Wakita, Takaji ^[12]; Perelson, Alan S. ^[14]; Dandri, Maura ^[15] ; Watashi, Koichi ^[16]; Iwami, Shingo ^[17]; Tanaka, Yasuhito ^[4]

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1. Nagoya Univ. (Japan); Pukyong National University (Korea, Republic of)
2. Nagoya Univ. (Japan); National Institute of Infectious Diseases, Tokyo (Japan)
3. Nagoya Univ. (Japan)
4. Kumamoto University (Japan)
5. Univ. of Oxford (United Kingdom)
6. Teine Keijinkai Hospital (Japan)
7. Nippon Medical School (Japan)
8. Chulalongkorn University (Thailand)
9. University Medical Center Hamburg-Eppendorf (Germany); Hamburg-Lu¨beck-Borstel-Riems (Germany)
10. Chiba University (Japan); RIKEN, Kanagawa (Japan)
11. Hokkaido University (Japan)
12. National Institute of Infectious Diseases, Tokyo (Japan)
13. University of Tokyo (Japan)
14. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
15. Chulalongkorn University (Thailand); University Medical Center Hamburg-Eppendorf (Germany)
16. National Institute of Infectious Diseases, Tokyo (Japan); Tokyo University of Sciences (Japan)
17. Nagoya Univ. (Japan); Kyushu University (Japan); Kyoto University (Japan); Japanese Foundation for Cancer Research (JFCR), Tokyo (Japan); RIKEN, Wako (Japan); Science Groove Inc., Fukuoka (Japan)

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.

• Research Organization: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
• Sponsoring Organization: USDOE; National Institutes of Health (NIH)
• Grant/Contract Number: 89233218CNA000001
• OSTI ID: 2556828
• Report Number(s): LA-UR--22-25182
• Journal Information: PLoS Computational Biology (Online), Journal Name: PLoS Computational Biology (Online) Journal Issue: 1 Vol. 21; ISSN 1553-7358
• Publisher: Public Library of Science
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
antiviral therapy
biopsy
hepatitis B virus
hepatocytes
viral kinetic modeling