Prediction of elimination of intrahepatic cccDNA in hepatitis B virus-infected patients by a combination of noninvasive viral markers

Evaluation of intrahepatic covalently closed circular DNA (cccDNA) is a key for searching an elimination of hepatitis B virus (HBV) infection. HBV RNA and HBV core-related antigen have been proposed as surrogate markers for evaluating cccDNA activity, although they do not necessarily estimate the am...

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Main Authors Iwami, Shingo, Iwamoto, Masashi, Wakita, Takaji, Watashi, Koichi, Perelson, Alan S, Tanaka, Yasuhito, Dandri, Maura, Aihara, Kazuyuki, Muramatsu, Masamichi, Iwami, Shinji, Kawakami, Eiryo, Allweiss, Lena, Tangkijvanich, Pisit, Chuaypen, Natthaya, Atsukawa, Masanori, Matsui, Takeshi, Tsukuda, Senko, Hayashi, Sanae, Kwang Su Kim, Kitagawa, Kosaku, Nishiyama, Takara, Nakamura, Naotoshi, Fujita, Yasuhisa
Format Paper
LanguageEnglish
Japanese
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 04.11.2022
Cold Spring Harbor Laboratory
Edition1.1
Subjects
Animal models
Biopsy
Cell culture
Circular DNA
Hepatitis B
Mathematical models
Microbiology
Patients
Propagation
RNA viruses
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Abstract Evaluation of intrahepatic covalently closed circular DNA (cccDNA) is a key for searching an elimination of hepatitis B virus (HBV) infection. HBV RNA and HBV core-related antigen have been proposed as surrogate markers for evaluating cccDNA activity, although they do not necessarily estimate the amount of cccDNA. Here, we developed a novel multiscale mathematical model describing intra- and inter-cellular viral propagation, based on the experimental quantification data in both HBV-infected cell culture and humanized mouse models. We applied it to HBV-infected patients under treatment and developed a model which can predict intracellular HBV dynamics only by use of noninvasive extracellular surrogate biomarkers. Importantly, the model prediction of the amount of cccDNA in patients over time was confirmed to be well correlated with the liver biopsy data. Thus, our noninvasive method enables to predict the amount of cccDNA in patients and contributes to determining the treatment endpoint required for elimination of intrahepatic cccDNA.Competing Interest StatementThe authors have declared no competing interest.
AbstractList Evaluation of intrahepatic covalently closed circular DNA (cccDNA) is a key for searching an elimination of hepatitis B virus (HBV) infection. HBV RNA and HBV core-related antigen have been proposed as surrogate markers for evaluating cccDNA activity, although they do not necessarily estimate the amount of cccDNA. Here, we developed a novel multiscale mathematical model describing intra- and inter-cellular viral propagation, based on the experimental quantification data in both HBV-infected cell culture and humanized mouse models. We applied it to HBV-infected patients under treatment and developed a model which can predict intracellular HBV dynamics only by use of noninvasive extracellular surrogate biomarkers. Importantly, the model prediction of the amount of cccDNA in patients over time was confirmed to be well correlated with the liver biopsy data. Thus, our noninvasive method enables to predict the amount of cccDNA in patients and contributes to determining the treatment endpoint required for elimination of intrahepatic cccDNA.Competing Interest StatementThe authors have declared no competing interest.
Evaluation of intrahepatic covalently closed circular DNA (cccDNA) is a key for searching an elimination of hepatitis B virus (HBV) infection. HBV RNA and HBV core-related antigen have been proposed as surrogate markers for evaluating cccDNA activity, although they do not necessarily estimate the amount of cccDNA. Here, we developed a novel multiscale mathematical model describing intra- and inter-cellular viral propagation, based on the experimental quantification data in both HBV-infected cell culture and humanized mouse models. We applied it to HBV-infected patients under treatment and developed a model which can predict intracellular HBV dynamics only by use of noninvasive extracellular surrogate biomarkers. Importantly, the model prediction of the amount of cccDNA in patients over time was confirmed to be well-correlated with the liver biopsy data. Thus, our noninvasive method enables to predict the amount of cccDNA in patients and contributes to determining the treatment endpoint required for elimination of intrahepatic cccDNA.
Author Watashi, Koichi
Perelson, Alan S
Kawakami, Eiryo
Hayashi, Sanae
Kitagawa, Kosaku
Allweiss, Lena
Wakita, Takaji
Aihara, Kazuyuki
Iwami, Shinji
Tangkijvanich, Pisit
Dandri, Maura
Nishiyama, Takara
Iwami, Shingo
Chuaypen, Natthaya
Atsukawa, Masanori
Iwamoto, Masashi
Nakamura, Naotoshi
Muramatsu, Masamichi
Matsui, Takeshi
Tsukuda, Senko
Kwang Su Kim
Tanaka, Yasuhito
Fujita, Yasuhisa
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2022, Posted by Cold Spring Harbor Laboratory
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Snippet Evaluation of intrahepatic covalently closed circular DNA (cccDNA) is a key for searching an elimination of hepatitis B virus (HBV) infection. HBV RNA and HBV...
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proquest
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SubjectTerms Animal models
Biopsy
Cell culture
Circular DNA
Hepatitis B
Mathematical models
Microbiology
Patients
Propagation
RNA viruses
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Title Prediction of elimination of intrahepatic cccDNA in hepatitis B virus-infected patients by a combination of noninvasive viral markers
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https://www.biorxiv.org/content/10.1101/2022.11.04.515164
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