Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance
- Loyola University Medical Center, Stritch School of Medicine, United States
- University of Barcelona, Spain
- University of Illinois, Chicago, United States
- Fred Hutchinson Cancer Research Center, United States
- Los Alamos National Laboratory, United States
Abstract
While the liver, specifically hepatocytes, are widely accepted as the main source of hepatitis C virus (HCV) production, the role of the liver/hepatocytes in clearance of circulating HCV remains unknown. Frequent HCV kinetic data were recorded and mathematically modeled from 5 liver-transplant patients throughout the anhepatic (absence of liver) phase and for 4 hours post-reperfusion. During the anhepatic phase, HCV remained at pre-anhepatic levels (n=3) or declined (n=2) with t1/2~1h. Immediately post-reperfusion, virus declined in a biphasic manner in 4 patients consisting of a rapid decline (t1/2=5min) followed by a slower decline (t1/2=67min). Consistent with the majority of patients in the anhepatic phase, when we monitored HCV clearance at 37°C from culture medium in the absence/presence of chronically infected hepatoma cells that were inhibited from secreting HCV, the HCV t1/2 in cell culture was longer in the absence of chronically HCV-infected cells. The results suggest that the liver plays a major role in the clearance of circulating HCV and that hepatocytes may be involved.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files
Article and author information
Author details
E Fabian Cardozo-Ojeda
Funding
National Institute of Allergy and Infectious Diseases (R01-AI078881)
- Susan L Uprichard
National Institute of Allergy and Infectious Diseases (R01-AI116868)
- Alan S Perelson
Instituto de Salud Carlos III (PI15/00151 and PI13/00155)
- Xavier Forns
Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (grant 2017_SGR_1753)
- Xavier Forns
CERCA Programme/Generalitat de Catalunya
- Xavier Forns
Germany Academic Exchange Service
- Tje Lin Chung
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Niel Hens, Hasselt University, Belgium
Ethics
Human subjects: The study was approved by the Ethics Committee at Hospital Clinic Barcelona (Record 2010/5810) and all patients provided a written informed consent.
Version history
- Preprint posted: August 4, 2020 (view preprint)
- Received: November 29, 2020
- Accepted: November 1, 2021
- Accepted Manuscript published: November 3, 2021 (version 1)
- Version of Record published: November 22, 2021 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance
eLife 10:e65297.
https://doi.org/10.7554/eLife.65297
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