Hepatitis C recurs rapidly after liver transplant

Extrahepatic sites may account for some viral replication

When a diseased liver is removed from a patient with Hepatitis C (HCV), serum viral levels plummet. However, after receiving a healthy liver transplant, virus 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 official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS). The journal is published on behalf of the societies by John Wiley & Sons, Inc. and is available online via Wiley InterScience (http://www.interscience.wiley.com/journal/livertransplantation).

Hepatitis C is the number one reason for liver transplantation, however, 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 which 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 antiviral 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."

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Article: "Kinetics of Hepatitis C Virus Reinfection After Liver Transplantation," Kimberly A. Powers, Ruy M. Ribeiro, Keyur Patel, Stephen Pianko, Lisa Nyberg, Paul Pockros, Andrew Conrad, John McHutchison, and Alan S. Perelson, Liver Transplantation; February 2006; (DOI: 10.1002/lt.20572).


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