Epstein-Barr Virus, Cytomegalovirus, and Other Viral Infections in Children After Liver Transplantatlon

Abstract

We studied 51 consecutive pediatric patients for the frequency and morbidity of viral infections after liver transplantation. The incidence of primary (67fT/o) and reactivation (480/0) Epstein-Barr virus (EBV) infections and reactivation (88fT/o) cytomegalovirus (CMV) infection was comparable to that seen in adult transplant recipients. However, fewer pediatric than adult transplant recipients experienced primary CMV infection (P < .01). Five (38%) of 13 CMV infections were symptomatic and included hepatitis, pneumonitis, enteritis, and mononucleosis. Two of 14 patients with primary EBV infection subsequently developed, at two months and two years after initial infection, an EBV-associated lymphoproliferative syndrome, and one of 10 patients with reactivated EBV infection developed a possible EBV-associated febrile encephalopathy. Other viruses causing infection in these children included herpes simplex virus, varicella-zoster virus, adenovirus, parainfluenza virus, respiratory syncytial virus, and rotavirus.Both Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are notable for their ubiquity, latency, and tendency to reactivate in the immunosuppressed host. Reports on the frequency and morbidity of EBV and CMV infections in adult transplant recipients from this center are available [1][2][3]. Comparable data in children have not been reported because, until recently, they had not undergone transplantations in large numbers. The behavior of EBV and CMV in pediatric transplant recipients is of interest not only because children may respond differently, but unlike adults, a large proportion of children have not been infected by these viruses before transplantation. Hence, a smaller number of children are at risk of developing reactivation infections; however, a greater number may be susceptible to primary infections and their consequent morbidity.

Immunizations and infectious diseases in pediatric liver transplantation

“…When transplants are performed in young patients, there is a high likelihood that they will be seronegative for CMV and EBV and therefore susceptible to primary infections, which are more severe than infections due to reactivation. 6,7 Donor-related issues represent another set of pretransplant factors. Transplant recipients are at risk for acquiring infections that may be active or latent within the donor organ.…”

“…Of particular concern is the use of anti-lymphocyte preparations, especially OKT3. 6,13,15 Newer anti-lymphocyte antibodies (eg, Thymoglobulin ® ) are also likely to be associated with an increased risk of infection.…”

“…The peak incidence of CMV infection occurs in this period. 6,13 However, the use of CMV prophylaxis has resulted in shifting the time of presentation of CMV disease so that some patients will present with this infection after 180 days. The intermediate period is also when patients begin to present with EBV-associated PTLD 7 and Pneumocystis jirovecii pneumonia (PCP).…”

Polymerase chain reaction and in situ hybridization of Epstein-Barr virus in liver biopsy specimens facilitate the diagnosis of EBV hepatitis after liver transplantation

“…The type of immunosuppression, in particular polyclonal and monoclonal antilymphocyte antibodies such as ATG or OKT3 that cause defects in T-cell immune surveillance of the virus, is a known risk factor for the development of EBV-related disorders after transplantation [12,19,33,381. In less immunosuppressed transplant recipients, primary EBV infection or reactivation may manifest itself with severe mononucleosis-like symptoms [6,7,26]. EBV-associated hepatitis after liver transplantation (LTX) can induce graft dysfunction and may be difficult to diagnose, due to lack of specific blood chemistry markers.…”

Detection of an early cytomegalovirus antigen with two‐color quantitative flow cytometry

“…Flow cytometry detected the viral antigen earlier than conventional immunofluorescent microscopy and cell culture for CMV cytopathological effect (CPE). Ten bronchoalveolar lavages assayed by flow cytometry and conventional diagnostic procedures demonstrated that flow cytometry might be useful in early diagnosis for CMV infection.Key terms: Monoclonal antibody, early virus antigen (CMV) detection of virus-infected cells Cytomegalovirus (CMV) infection has been recognized as a significant cause of morbidity and mortality in bone marrow, cardiac, and renal transplant patients as well as in patients with human immunodeficiency virus (HIV) infections (1,(3)(4)(5)10,19,21,22). Traditionally, CMV infection has been demonstrated by virus isolation and identification in cell culture or by the finding of pathognomonic inclusion bodies in biopsy specimens (9).…”