Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study

Liver transplantation is the only curative treatment of end-stage liver disease, and every year, around 60 patients undergo liver transplantation in Denmark. Immunosuppressive therapy is necessary to avoid rejection of the transplanted organ. Over 90% of adults have been infected with at least one herpesvirus, and it is characteristic for herpesviruses that after a first-time infection, the virus remains dormant in the body and may reactivate, particularly if the host is immunosuppressed. An effective immune response against reactivation depends highly on T cells, but T cells are suppressed by immunosuppressive drugs given to organ transplant recipients. Infections caused by herpesviruses are therefore very common in organ transplant recipients, and particularly two herpesviruses, cytomegalovirus (CMV) and varicella-zoster virus (VZV) pose challenges after transplantation. CMV causes significant morbidity in transplant recipients, contributes to increased mortality and may contribute to loss of the transplanted organ. CMV infections occur in around 40% of liver transplant recipients within a year of transplantation. VZV causes chickenpox at first-time infection and shingles at reactivation. VZV is the second-most common infection in transplant recipients and occurs in around 9% of liver transplant recipients each year. Organ transplant recipients are at higher risk for disseminated disease with complications compared to immunocompetent persons. A limited number of drugs exist that reduce the risk of and treat CMV infection, but they may cause significant adverse events, and drug resistance is emerging. To avoid CMV infection, some liver transplant recipients receive prophylactic therapy, but due to toxicity, new treatment modalities are warranted. This requires knowledge about herpesvirus specific T cell function in liver transplant recipients, which currently is limited. The aim of this study is to provide an in-depth description of the protective immune response and immunological risk factors for CMV and VZV infections in liver transplant recipients and to identify patients at high risk in order to provide a platform for future treatment modalities against CMV and VZV infections in liver transplant recipients.