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Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy

Methodology for accurate quantification of intra-hepatic cccDNA has long been a technical challenge, yet it is highly desired in the clinic. Here, we developed a sensitive method for quantification of intrahepatic cccDNA in liver biopsies from patients, which allowed to predict patient’s response to...

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Autores principales: Mu, Di, Yuan, Fang-Chao, Chen, Yu, Jiang, Xiao-Yan, Yan, Liang, Jiang, Ling-Yu, Gong, Jian-Ping, Zhang, Da-Zhi, Ren, Hong, Liao, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517439/
https://www.ncbi.nlm.nih.gov/pubmed/28725013
http://dx.doi.org/10.1038/s41598-017-05242-y
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author Mu, Di
Yuan, Fang-Chao
Chen, Yu
Jiang, Xiao-Yan
Yan, Liang
Jiang, Ling-Yu
Gong, Jian-Ping
Zhang, Da-Zhi
Ren, Hong
Liao, Yong
author_facet Mu, Di
Yuan, Fang-Chao
Chen, Yu
Jiang, Xiao-Yan
Yan, Liang
Jiang, Ling-Yu
Gong, Jian-Ping
Zhang, Da-Zhi
Ren, Hong
Liao, Yong
author_sort Mu, Di
collection PubMed
description Methodology for accurate quantification of intra-hepatic cccDNA has long been a technical challenge, yet it is highly desired in the clinic. Here, we developed a sensitive method for quantification of intrahepatic cccDNA in liver biopsies from patients, which allowed to predict patient’s response to interferon therapy at baseline. Twenty-five patients with HBeAg+ CHB were recruited and liver biopsies were obtained at baseline and 1-year after interferon treatment, respectively. Both intrahepatic cccDNA and HBV DNA were absolutely quantified by a droplet digital PCR amplification system. Patients were categorized as either responder or non-responder group based on their HBeAg status 1-year after interferon therapy. Levels of both intrahepatic HBV DNA and HBV cccDNA were significantly reduced after interferon treatment among the responders, but not the non-responders, in comparison with their levels at baseline. Baseline values of intrahepatic HBV DNA over cccDNA significantly correlated with patient’s response to PEG-IFN therapy (P = 0.000). In addition, HBeAg seroconversion also correlates with a significant reduction in intrahepatic pgRNA production among the responders after interferon therapy (P = 0.030). In conclusion, our results suggest that baseline value of intrahepatic HBV DNA over cccDNA may be a preferable indicator for selecting appropriate patients for IFN-based therapy in the clinic.
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spelling pubmed-55174392017-07-20 Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy Mu, Di Yuan, Fang-Chao Chen, Yu Jiang, Xiao-Yan Yan, Liang Jiang, Ling-Yu Gong, Jian-Ping Zhang, Da-Zhi Ren, Hong Liao, Yong Sci Rep Article Methodology for accurate quantification of intra-hepatic cccDNA has long been a technical challenge, yet it is highly desired in the clinic. Here, we developed a sensitive method for quantification of intrahepatic cccDNA in liver biopsies from patients, which allowed to predict patient’s response to interferon therapy at baseline. Twenty-five patients with HBeAg+ CHB were recruited and liver biopsies were obtained at baseline and 1-year after interferon treatment, respectively. Both intrahepatic cccDNA and HBV DNA were absolutely quantified by a droplet digital PCR amplification system. Patients were categorized as either responder or non-responder group based on their HBeAg status 1-year after interferon therapy. Levels of both intrahepatic HBV DNA and HBV cccDNA were significantly reduced after interferon treatment among the responders, but not the non-responders, in comparison with their levels at baseline. Baseline values of intrahepatic HBV DNA over cccDNA significantly correlated with patient’s response to PEG-IFN therapy (P = 0.000). In addition, HBeAg seroconversion also correlates with a significant reduction in intrahepatic pgRNA production among the responders after interferon therapy (P = 0.030). In conclusion, our results suggest that baseline value of intrahepatic HBV DNA over cccDNA may be a preferable indicator for selecting appropriate patients for IFN-based therapy in the clinic. Nature Publishing Group UK 2017-07-19 /pmc/articles/PMC5517439/ /pubmed/28725013 http://dx.doi.org/10.1038/s41598-017-05242-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mu, Di
Yuan, Fang-Chao
Chen, Yu
Jiang, Xiao-Yan
Yan, Liang
Jiang, Ling-Yu
Gong, Jian-Ping
Zhang, Da-Zhi
Ren, Hong
Liao, Yong
Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy
title Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy
title_full Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy
title_fullStr Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy
title_full_unstemmed Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy
title_short Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy
title_sort baseline value of intrahepatic hbv dna over cccdna predicts patient’s response to interferon therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517439/
https://www.ncbi.nlm.nih.gov/pubmed/28725013
http://dx.doi.org/10.1038/s41598-017-05242-y
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