Rate of hepatitis C viral clearance by human livers in human patients

Liver transplantation modeling primary infection and implications for studying entry inhibition

Michael G. Hughes, William W. Tucker, Sreelatha Reddy, Michael E. Brier, David Koch, Craig J. McClain, Colleen Jonsson, Nobuyuki Matoba, Donghoon Chung

Research output: Contribution to journalArticle

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). 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.

Original languageEnglish (US)
Article numbere0180719
JournalPLoS ONE
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

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hepatitis C
liver transplant
Hepatitis C virus
Hepatitis C
Viruses
Hepacivirus
Liver
Liver Transplantation
liver
Infection
infection
Reperfusion
Transplants
allografting
immunosuppression
blood serum
Immunosuppression
half life
Allografts
Half-Life

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Rate of hepatitis C viral clearance by human livers in human patients : Liver transplantation modeling primary infection and implications for studying entry inhibition. / Hughes, Michael G.; Tucker, William W.; Reddy, Sreelatha; Brier, Michael E.; Koch, David; McClain, Craig J.; Jonsson, Colleen; Matoba, Nobuyuki; Chung, Donghoon.

In: PLoS ONE, Vol. 12, No. 7, e0180719, 01.07.2017.

Research output: Contribution to journalArticle

Hughes, Michael G. ; Tucker, William W. ; Reddy, Sreelatha ; Brier, Michael E. ; Koch, David ; McClain, Craig J. ; Jonsson, Colleen ; Matoba, Nobuyuki ; Chung, Donghoon. / Rate of hepatitis C viral clearance by human livers in human patients : Liver transplantation modeling primary infection and implications for studying entry inhibition. In: PLoS ONE. 2017 ; Vol. 12, No. 7.
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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). 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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