Cyclosporine Inhibits Hepatitis C Virus In Vitro

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Source: Wiley & Sons, Inc.

Date: 2006-01-06

Cyclosporine Inhibits Hepatitis C Virus In Vitro

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

Wiley & Sons, Inc. and is available online via Wiley InterScience

(http:/ & #8203;/ & #8203;www.interscience.wiley.com/ & #8203;journal/ & #8203;livertran\

splantation).

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 o 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. "

o J. Firpi, Haizhen Zhu, Giuseppe Morelli, Manal F. Abdelmalek,

Consuelo Soldevilla-Pico, Victor I. Machicao, Roniel Cabrera, Alan I. ,

Chen Liu, and R. , Liver Transplantation; January 2006; (DOI:

10.1002/lt.20532).

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This story has been adapted from a news release issued by Wiley & Sons,

Inc..

http://www.sciencedaily.com/releases/2006/01/060106002034.htm#

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