Heart transplant rejections in children tied to virus
Rejection of transplanted hearts in children has been found to be associated with the presence of a virus, according to an article in this week's New England Journal of Medicine, published Thursday.
Girish
S. Shirali, M.D., director of pediatric echocardiography, is
first author of the paper entitled Viral Genome with Post-transplantation
Coronary Arterio-pathy and Graft Loss in Children after Cardiac Transplantation.
Shirali extracted 553 heart tissue samples from 149 pediatric heart transplant patients at Loma Linda University, where he was working at the time.
The tissue was taken in conjunction with biopsies routinely performed following heart transplant surgery. Shirali sent the samples to Baylor University Medical Center in Houston where Jeffrey A. Towbin, M.D., and his colleagues performed polymerase chain reaction (PCR) analysis on the samples to determine the presence of viruses. Shirali performed clinical follow-up on the patients. The data from the PCR analysis and the clinical follow-up were sent to a statistician at the University of Washington in Seattle for analysis.
Based on the data, the researchers came to the conclusion that the presence of certain viruses, especially adenovirus, in heart tissue of pediatric transplant recipients is predictive of adverse clinical events, including rejection of the transplanted heart and coronary artery disease. In transplant patients, the coronary artery disease occurs in smaller vessels, making the condition not correctable, and often leading to death.
The researchers found that for patients with a negative PCR test, indicating viruses were not present in the heart tissue, the five-year graft-survival rate was 96.2 percent; whereas for patients with positive results on the PCR test, the rate was 64.7 percent.
“This is a significant difference, especially put in the context of the human and emotional costs for families whose children have received life-saving heart transplants,” said Shirali.
“The message of this paper is that because of the real increase in mortality found with viral infection, we need to be more aggressive in treating patients following a heart transplant,” he said.
“Every time we do a biopsy on a transplant patient, we need to look for viruses, and perhaps we should do biopsies more frequently. As soon as we discover the presence of a virus through a positive PCR test, we know that these are the kids who are at risk. This sometimes occurs before there is any other sign of rejection, and this may be the time to attempt to boost the immune system through the administration of gamma globulin.”
The study also has important implications for future research initiatives. It suggests the importance of the development of antiviral agents and vaccines for pediatric heart transplant patients. It also suggests future investigation to determine whether the finding are applicable to other transplant patients.
Another profound implication is that if viral infection is associated with coronary artery disease after heart transplant, can viral infection be associated with coronary artery disease in someone who has never had a heart transplant. These are intriguing areas that merit future study, according to Shirali.
Shirali's co-authors on the paper are Jeffrey Towbin, M.D., Jiyuan Ni,
M.D., and Neil E. Bowles, Ph.D., of Baylor College of Medicine; Richard
E. Chinnock, M.D. and Joyce K. Johnston of Loma Linda University Children's
Hospital; and Geoffrey L. Rosenthal, M.D., Ph.D., of the University of
Washington in Seattle.