A quantitative systems pharmacology model for acute viral hepatitis B.

Autor:	Asín-Prieto E; Pharmacometrics & Systems Pharmacology Lab, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, C/Irunlarrea 1, University of Navarra, Pamplona 31080, Spain.; IdiSNA, Navarra Institute for Health Research, C/Irunlarrea 3, 31008 Pamplona, Spain., Parra-Guillen ZP; Pharmacometrics & Systems Pharmacology Lab, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, C/Irunlarrea 1, University of Navarra, Pamplona 31080, Spain.; IdiSNA, Navarra Institute for Health Research, C/Irunlarrea 3, 31008 Pamplona, Spain., Gómez Mantilla JD; Pharmacometrics & Systems Pharmacology Lab, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, C/Irunlarrea 1, University of Navarra, Pamplona 31080, Spain.; IdiSNA, Navarra Institute for Health Research, C/Irunlarrea 3, 31008 Pamplona, Spain., Vandenbossche J; Global Clinical Pharmacology, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Stuyckens K; Global Clinical Pharmacology, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium., de Trixhe XW; Global Clinical Pharmacology, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Perez-Ruixo JJ; Global Clinical Pharmacology, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Troconiz IF; Pharmacometrics & Systems Pharmacology Lab, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, C/Irunlarrea 1, University of Navarra, Pamplona 31080, Spain.; IdiSNA, Navarra Institute for Health Research, C/Irunlarrea 3, 31008 Pamplona, Spain.
Jazyk:	angličtina
Zdroj:	Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2021 Sep 02; Vol. 19, pp. 4997-5007. Date of Electronic Publication: 2021 Sep 02 (Print Publication: 2021).
DOI:	10.1016/j.csbj.2021.08.052
Abstrakt:	Hepatitis B liver infection is caused by hepatitis B virus (HBV) and represents a major global disease problem when it becomes chronic, as is the case for 80-90% of vertical or early life infections. However, in the vast majority (>95%) of adult exposures, the infected individuals are capable of mounting an effective immune response leading to infection resolution. A good understanding of HBV dynamics and the interaction between the virus and immune system during acute infection represents an essential step to characterize and understand the key biological processes involved in disease resolution, which may help to identify potential interventions to prevent chronic hepatitis B. In this work, a quantitative systems pharmacology model for acute hepatitis B characterizing viral dynamics and the main components of the innate, adaptive, and tolerant immune response has been successfully developed. To do so, information from multiple sources and across different organization levels has been integrated in a common mechanistic framework. The final model adequately describes the chronology and plausibility of an HBV-triggered immune response, as well as clinical data from acute patients reported in the literature. Given the holistic nature of the framework, the model can be used to illustrate the relevance of the different immune pathways and biological processes to ultimate response, observing the negligible contribution of the innate response and the key contribution of the cellular response on viral clearance. More specifically, moderate reductions of the proliferation of activated cytotoxic CD8+ lymphocytes or increased immunoregulatory effects can drive the system towards chronicity. Competing Interests: 6At the time the research was performed, EASP, ZPPG, JDGM and IFT received research funding from Janssen Research & Development; no grant number is applicable. JV, KS, XWT, and JJPR are employed by Janssen Pharmaceuticals.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2021 The Author(s).)
Databáze:	MEDLINE
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