Kinetics of hepatitis C virus reinfection after liver transplantation.
Improved understanding of hepatitis C virus (HCV) dynamics during and after liver transplantation can be useful in optimizing antiviral therapy in transplant recipients. We analyzed serum HCV ribonucleic acid (RNA) levels during and after cadaveric liver transplantation in 6 HCV patients. After removal of the liver and before the new liver started producing virions, HCV RNA levels dropped with an average half-life (t(1/2)) of 0.8 hours. Viral loads then continued to drop up to 23 hours postimplantation (t(1/2) = 3.4 hours), and began to rise (doubling-time = 2.0 days) as soon as 15 hours after the anhepatic phase. In 3 patients the viral load reached a plateau before rising, suggesting that a nonhepatic source supplied virions and balanced their intrinsic clearance. However, from the decline in viral load over the first 24 hours of the postanhepatic phase, we estimate that nonhepatic sources can at most correspond to 4% of total viral production, 96% of which occurs in the liver, even after we corrected for fluid exchanges during surgery. As the new liver was reinfected, production increased and viral load rose to a new steady state. Using nonlinear regression, we were able to fit the patients' HCV RNA data to a viral dynamic model and estimate the de novo infection rate (mean 1.5 x 10(-6) mL/virion/day), as well as the average percentage of hepatocytes infected at the posttransplantation steady state (19%). In conclusion, we have quantified liver reinfection dynamics in the absence of posttransplantation antiviral therapy. Our findings support the notion that early antiviral therapy may delay or prevent reinfection.
Powers
Kimberly A
KA
Theoretical Biology & Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Ribeiro
Ruy M
RM
Patel
Keyur
K
Pianko
Stephen
S
Nyberg
Lisa
L
Pockros
Paul
P
Conrad
Andrew J
AJ
McHutchison
John
J
Perelson
Alan S
AS
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006084:Graft Rejection / Q000821:virology; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis; D006801:Humans; D016014:Linear Models; D017093:Liver Failure / Q000209:etiology / Q000601:surgery*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000821:virology*; D011336:Probability; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis*; D018570:Risk Assessment; D055502:Secondary Prevention; D014779:Virus Replication
D015415:Biomarkers; D012367:RNA, Viral