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

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 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.

Original languageEnglish
Article numbere65297
JournaleLife
Volume10
DOIs
StatePublished - 3 Nov 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
‍© Shekhtman et al.

Funding

The study was supported, in part, by U.S. National Institute of Health grants, R01-AI078881, R01-OD011095, R01GM121600, and R01-AI116868, Instituto de Salud Carlos III (PI15/00151 and PI13/00155,cofunded by the European Regional Development Fund [ERDF]) and by Secretaria d’Uni-versitats i Recerca del Departament d’Economia i Coneixement (grant 2017_SGR_1753) and CERCA Programme/Generalitat de Catalunya, and Germany Academic Exchange Service.

FundersFunder number
CERCA Programme/Generalitat de Catalunya, and Germany Academic Exchange Service
Secretaria d’Uni-versitats i Recerca del Departament d’Economia i Coneixement
National Institutes of HealthR01-AI078881, R01-AI116868, R01-OD011095
National Institute of General Medical SciencesR01GM121600
Instituto de Salud Carlos IIIPI13/00155, PI15/00151
European Regional Development Fund2017_SGR_1753

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