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Rate of hepatitis C viral clearance by human livers in human patients: Liver transplantation modeling primary infection and implications for studying entry inhibition.
- Source :
- PLoS ONE, Vol 12, Iss 7, p e0180719 (2017)
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- To better understand the dynamics of early hepatitis C virus (HCV) infection, we determined how rapidly non-cirrhotic HCV-uninfected liver allografts clear HCV from the circulation of cirrhotic HCV-infected patients at the time of transplantation but before administration of immunosuppression. Specifically, we characterized serum HCV kinetics during the first 90 min of reperfusion for 19 chronically HCV-infected patients transplanted with an HCV-uninfected liver by measuring serum viral load immediately prior to reperfusion (t = 0) and then every 15 min for a total of 90 min (t = 90). Immunosuppression was withheld until all samples were taken to better model primary infection. During this period, rates of viral clearance varied more than 20-fold with a median rate constant of 0.0357 1/min, range 0.0089-0.2169; half-life (minutes) median 19.4, range 3.2-77.8. The majority of viral clearance occurred within the first 60 min. The amount of blood transfused during this 90-min period (a potential confounding variable of this human liver transplant model of primary infection) accounted for 53% and 59% of k (r = 0.53, p = 0.05) and half-life (r = 0.59, p = 0.03) variability, respectively. No other clinical variables tested (age, allograft weight, and degree of reperfusion injury as assessed by peak postoperative ALT or AST) accounted for the remaining variability (p>0.05).In a human liver transplant model of primary infection, HCV rapidly clears the bloodstream. With approximately 90% of clearance occurring in the first 90 minutes of reperfusion, studies of HCV entry inhibition could utilize rate of clearance during this early period as an outcome measure.
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.9c24ef0ab0428081b4a22c25415617
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pone.0180719