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Hepatitis
C Recurs Rapidly after Liver Transplant
When a diseased liver is removed
from a patient with hepatitis C, serum HCV levels
(HCV RNA) decline quickly and significantly. However, after receiving
a healthy liver
transplant, HCV levels rebound and can surpass pre-transplant levels
within a few days, according to a new study published in the February 2006 issue
of Liver Transplantation. The journal is available online via Wiley
InterScience.
 Hepatitis
C is the number one reason for liver transplantation in the US. Unfortunately,
the virus always recurs in the new liver. Since mathematical models have been
useful in the study of the viral dynamics of HIV and hepatitis B, researchers,
led by Kimberly A. Powers and Ruy M. Ribeiro of the Los Alamos National Laboratory in New Mexico, sought to use
a mathematical model to quantify the liver reinfection
dynamics of HCV.
The researchers, in collaboration with a surgical team
lead by John McHutchison now at Duke University
Medical Center,
followed six HCV-infected patients who received cadaveric
liver transplants. They collected blood samples before, during and after transplantation
to assess changing levels of HCV RNA that was measured using reverse transcription
polymerase chain reaction assay. They then plugged the data into a mathematical
model, correcting for fluid balance, and analyzed the results using linear regression.
“In most patients,” the authors report, “HCV RNA levels decreased rapidly
during and after transplantation and subsequently began to increase – reaching
above pre-transplant levels in all but one patient – within a few days of the
procedure.” They found that when the diseased liver was removed, virus levels
dropped with an average half-life of 48 minutes. After the new liver was implanted,
they found that virus levels continued to drop for up to 23 hours, then began
to rise, doubling every 2 days.
Notably, in three patients, the virus
levels plateaued before rising, suggesting, say the
authors “that a non-hepatic source supplied virions and balanced their intrinsic clearance.” The authors
estimate, however, that non-hepatic sources can only account for 4 percent of
total viral production. Ninety-six percent of it occurs in the liver.
The patterns of viremia decline and increase seen in
this study are consistent with previous studies, although this study indicates
a much faster virion half-life than previously suggested.
The findings also support the notion that HCV can replicate rapidly in the post-transplant
immunosuppressed patient, leading the authors to suggest
that early anti-HCV therapy may delay or prevent reinfection.
The study was limited by the
small number of patients and the single compartment model, which did not separately
account for liver and extrahepatic sites of viral replication. “Nevertheless,” report
the authors, “the rapid HCV RNA decline in the anhepatic
phase, followed by the postoperative increase observed in several patients…suggest
that the liver is the primary site of viral replication, with at most small contributions
from extrahepatic sites.”
In conclusion, the authors
write, “Continued work towards elucidating extrahepatic replication, the time-course of reinfection, the effects of immunosuppressive therapy, and
the relationships among viremia, infection and liver
damage will be beneficial in optimizing treatment for HCV patients undergoing
liver transplantation.” 02/03/06 Reference
K A Powers and others. Kinetics
of Hepatitis C Virus Reinfection after Liver Transplantation.
Liver Transplantation 12(2): 207-216. February 2006.
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