4.8 Article

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

期刊

ELIFE
卷 10, 期 -, 页码 -

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eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.65297

关键词

hepatitis C virus; viral kinetics; hepatocytes; mathematical modeling; liver transplant; cell culture; Human

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资金

  1. National Institute of Allergy and Infectious Diseases [R01-AI078881, R01-AI116868]
  2. Instituto de Salud Carlos III [PI15/00151, PI13/00155]
  3. Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement grant [2017_SGR_1753]
  4. CERCA Programme/Generalitat de Catalunya
  5. Germany Academic Exchange Service Tje Lin Chung National Institute of General Medical Sciences [R01GM121600]
  6. National Institutes of Health [R01-OD011095]

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This study found that the liver plays a major role in the clearance of circulating HCV, with hepatocytes potentially involved. Through analysis of dynamic data and mathematical modeling from liver transplant patients, the process of HCV clearance was investigated.
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 t(1/2)similar to 1 hr. Immediately post-reperfusion, virus declined in a biphasic manner in four patients consisting of a rapid decline (t(1/2) = 5 min) followed by a slower decline (t(1/2) = 67 min). Consistent with the majority of patients in the anhepatic phase, when we monitored HCV clearance at 37 degrees C from culture medium in the absence/presence of chronically infected hepatoma cells that were inhibited from secreting HCV, the HCV t(1/2) 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.

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