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...

Descripción completa

Guardado en:
Detalles Bibliográficos
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:
R
Q
Acceso en línea:https://doaj.org/article/88ec9d007d544a56ba1441581f7bf611
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario: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.