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PUBLIC RELEASE DATE:
31-Jul-2008

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Contact: Sean Wagner
swagner@wiley.com
781-388-8550
Wiley

Antiviral therapy helps children at risk for post-transplant lymphoproliferative disease

The antiviral drug, valganciclovir, can lower the levels of Epstein-Barr virus in children with liver transplants, according to a new study. About half of young transplant recipients with detectable levels of the virus in their blood responded to a long course of the therapy, with 60 percent maintaining their response when they stopped taking the drug. These findings are in the August issue of Liver Transplantation, a journal by John Wiley & Sons. The article is also available online at Wiley Interscience (www.interscience.wiley.com).

Many pediatric liver recipients become infected with Epstein-Barr virus post-transplant, probably because the latent virus is in lymphocytes in the graft or in blood derivatives. Immunosuppressants taken to control rejection change the children's normal immune response to the virus, leading in some cases to uncontrolled lymphocyte B proliferation. Antiviral therapy is one possible way to address the danger of Epstein-Barr infection in transplant recipients.

Researchers, led by Paloma Jara of Madrid, studied the effects of valganciclovir in 47 pediatric transplant recipients with detectable Epsten-Barr DNA in their blood. They hoped to decrease the risk of post-transplant lymphoproliferative disease (PTLD) by blocking the viral replication that can lead to lymphocyte B proliferation.

After a median 8 months of treatment, EBV-DNA became undetectable in about half of the children who were asymptomatic at the start of the therapy, and no new cases of PTLD developed. In one child, who started the study with suspected PTLD, symptoms worsened over the course of the study. The safety profile was excellent, with no severe adverse events attributed to the drug.

The authors suggest that their results be interpreted with caution as they did not include a control group, and because the short timeframe for follow-up yielded no definitive conclusions about EBV outcomes.

Still, they concluded, "Valganciclovir has been shown safe in the current study and the population of children treated did not develop PTLD, warranting future trials to confirm a positive effect in the management of EBV infection."

In an accompanying editorial, Michael Green and George Mazariegos of the University of Pittsburgh, discuss their experience lowering immune suppression for patients with persistently high EBV loads, instead of using antiviral therapy.

"We have developed a relatively standardized approach to the presence of the high load carrier state which aims to gradually reduce immune suppression while carefully monitoring for any evidence of breakthrough rejection," they report.

"We agree that additional trials of valganciclovir are needed to establish a beneficial effect of this drug," they conclude.

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