Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance

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 five liver transplant pa...

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Autores principales:	Louis Shekhtman, Miquel Navasa, Natasha Sansone, Gonzalo Crespo, Gitanjali Subramanya, Tje Lin Chung, E Fabian Cardozo-Ojeda, Sofía Pérez-del-Pulgar, Alan S Perelson, Scott J Cotler, Xavier Forns, Susan L Uprichard, Harel Dahari
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	hepatitis C virus viral kinetics hepatocytes mathematical modeling liver transplant cell culture Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/88ec9d007d544a56ba1441581f7bf611
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spelling	oai:doaj.org-article:88ec9d007d544a56ba1441581f7bf6112021-11-22T13:16:42ZModeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance10.7554/eLife.652972050-084Xe65297https://doaj.org/article/88ec9d007d544a56ba1441581f7bf6112021-11-01T00:00:00Zhttps://elifesciences.org/articles/65297https://doaj.org/toc/2050-084XWhile 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 five liver transplant patients throughout the anhepatic (absence of liver) phase and for 4 hr post-reperfusion. During the anhepatic phase, HCV remained at pre-anhepatic levels (n = 3) or declined (n = 2) with t1/2~1 hr. Immediately post-reperfusion, virus declined in a biphasic manner in four patients consisting of a rapid decline (t1/2 = 5 min) followed by a slower decline (t1/2 = 67 min). 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.Louis ShekhtmanMiquel NavasaNatasha SansoneGonzalo CrespoGitanjali SubramanyaTje Lin ChungE Fabian Cardozo-OjedaSofía Pérez-del-PulgarAlan S PerelsonScott J CotlerXavier FornsSusan L UprichardHarel DaharieLife Sciences Publications Ltdarticlehepatitis C virusviral kineticshepatocytesmathematical modelingliver transplantcell cultureMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatitis C virus viral kinetics hepatocytes mathematical modeling liver transplant cell culture Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	hepatitis C virus viral kinetics hepatocytes mathematical modeling liver transplant cell culture Medicine R Science Q Biology (General) QH301-705.5 Louis Shekhtman Miquel Navasa Natasha Sansone Gonzalo Crespo Gitanjali Subramanya Tje Lin Chung E Fabian Cardozo-Ojeda Sofía Pérez-del-Pulgar Alan S Perelson Scott J Cotler Xavier Forns Susan L Uprichard Harel Dahari Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance
description	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 five liver transplant patients throughout the anhepatic (absence of liver) phase and for 4 hr post-reperfusion. During the anhepatic phase, HCV remained at pre-anhepatic levels (n = 3) or declined (n = 2) with t1/2~1 hr. Immediately post-reperfusion, virus declined in a biphasic manner in four patients consisting of a rapid decline (t1/2 = 5 min) followed by a slower decline (t1/2 = 67 min). 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.
format	article
author	Louis Shekhtman Miquel Navasa Natasha Sansone Gonzalo Crespo Gitanjali Subramanya Tje Lin Chung E Fabian Cardozo-Ojeda Sofía Pérez-del-Pulgar Alan S Perelson Scott J Cotler Xavier Forns Susan L Uprichard Harel Dahari
author_facet	Louis Shekhtman Miquel Navasa Natasha Sansone Gonzalo Crespo Gitanjali Subramanya Tje Lin Chung E Fabian Cardozo-Ojeda Sofía Pérez-del-Pulgar Alan S Perelson Scott J Cotler Xavier Forns Susan L Uprichard Harel Dahari
author_sort	Louis Shekhtman
title	Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance
title_short	Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance
title_full	Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance
title_fullStr	Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance
title_full_unstemmed	Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance
title_sort	modeling hepatitis c virus kinetics during liver transplantation reveals the role of the liver in virus clearance
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/88ec9d007d544a56ba1441581f7bf611
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Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance

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