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A quantitative systems pharmacology model for acute viral hepatitis B

  • Asín-Prieto, Eduardo1, 2
  • Parra-Guillen, Zinnia P.1, 2
  • Gómez Mantilla, José David1, 2
  • Vandenbossche, Joris3
  • Stuyckens, Kim3
  • de Trixhe, Xavier Woot3
  • Perez-Ruixo, Juan José3
  • Troconiz, Iñaki F.1, 2
  • 1 Pharmacometrics & Systems Pharmacology Lab, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, C/Irunlarrea 1, University of Navarra, Pamplona 31080, Spain
  • 2 IdiSNA, Navarra Institute for Health Research, C/Irunlarrea 3, 31008 Pamplona, Spain
  • 3 Global Clinical Pharmacology, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium
Published Article
Computational and Structural Biotechnology Journal
Publication Date
Sep 02, 2021
DOI: 10.1016/j.csbj.2021.08.052
PMID: 34589180
PMCID: PMC8449028
PubMed Central
  • Research Article


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.

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