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| http://www.sciencedaily.com/release...60106002034.htm
Liver transplant patients with hepatitis C virus (HCV) achieved significantly
better long-term viral response when taking the immunosuppressive agent
Cyclosporine along with interferon-ribavirin combination therapy. Cyclosporine
also showed efficacy against Hepatitis C virus in vitro.
The results of this study appear in the January 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/j...transplantation).
Hepatitis C always recurs after liver transplantation, often damaging the new
organ and rendering patients ineligible for retransplantation. To address this
problem, patients with hepatitis C often undergo interferon-ribavirin
combination therapy after receiving a liver transplant in hopes of a sustained
virologic response. At the same time, of course, the patients must take
immunosuppressive agents to guard against transplant rejection.
The most commonly used anti-rejection medication is Tacrolimus, although
Cyclosporine is also used. The latter drug has been shown to have anti-viral
activity against HIV, herpes simplex and vaccinia virus, leading researchers to
speculate it might also inhibit hepatitis C virus. To examine this hypothesis,
they analyzed the impact of the drug in a liver transplant population. They also
studied its effect on hepatitis C in vitro.
For the in vitro study, the researchers, led by Roberto J. Firpi, M.D. of the
University of Florida, treated the HCV replicon line, GSB1, with varying doses
of Cyclosporine for 48 hours and examined the results. They found that
Cyclosporine reduced HCV replication by 20 percent, compared to no reduction
with Tacrolimus. Furthermore, the Cyclosporine appeared to work through a
different pathway compared to interferon.
Then, the researchers retrospectively examined the cases of 115 people infected
with hepatitis C who had undergone liver transplantation at the university of
Florida between 1991 and November 2002 and had received interferon-based therapy
alongside their anti-rejection medications. After 48 weeks, 46 percent of the
patients taking Cyclosporine had achieved a sustained virological response,
compared with just 27 percent of the patients taking Tacrolimus.
"Our study suggests that Cyclosporine may play a beneficial role as primary
immunosuppression for patients transplanted for HCV infection and may offer an
advantage to Tacrolimus in those patients undergoing IFN-based therapy," the
authors report. In addition, they confirm antiviral activity by the drug in cell
cultures, having found that, "combination of Cyclosporine and interferon achieve
better antiviral effect than either one alone."
Of note, considerably more patients taking Tacrolimus had to reduce or stop the
therapy due to side effects. Also of possible significance, more patients taking
Cyclosporine died, mostly due to infections and hepatitis complications, though
this may be attributable to a longer follow-up period for that group.
Still, the indication that Cyclosporine had novel antiviral properties invites
further investigation, the authors write. A prospective randomized comparative
trial between cyclosporine and TAC should further evaluate their observations.
"Due to the accelerated rate of disease progression and graft failure after
liver transplantation in HCV patients," the authors conclude, "it will be very
important to determine the ideal immunosuppression regimen."
###
Article: "Cyclosporine Suppresses Hepatitis C Virus In Vitro and Increases the
Chance of a Sustained Virological Response After Liver Transplantation." Roberto
J. Firpi, Haizhen Zhu, Giuseppe Morelli, Manal F. Abdelmalek, Consuelo
Soldevilla-Pico, Victor I. Machicao, Roniel Cabrera, Alan I. Reed, Chen Liu, and
David R. Nelson, Liver Transplantation; January 2006; (DOI: 10.1002/lt.20532).
http://www.sciencedaily.com/release...60106002034.htm
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