Journal
PLOS ONE
Volume 12, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0180719
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Funding
- American Society of Transplant Surgeons
- American Association for the Study of Liver Diseases
- ASTS Roche Surgical Scientist Scholarship
- ASTS Team Donate Life Junior Faculty Award
- AASLD Career Development Award in Liver in Transplantation
- NIH through an institutional KL2 at the Medical University of South Carolina
- American Society of Transplant Surgeons Team Donate Life Junior Faculty Award
- American Association for the Study of Liver Diseases Career Development Award in Liver Transplantation
- National Institutes of Health [KL2 1KL2RR029880-01]
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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). Conclusion: 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.
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