Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 80
- 试验地点
- 6
- 主要终点
- Frequency, phenotype and function of CMV- and VZV-specific T cells (descriptive)
研究概览
简要总结
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.
详细描述
The Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study (HISTORY) is a prospective cohort study that aims to provide in-depth characterisation 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 of infection based on clinical and immunological risk factors. All adult patients enlisted for liver transplantation at the Copenhagen University Hospital - Rigshospitalet will be invited to participate regardless of indication for transplantation.
At study entry, participants will fill out a questionnaire regarding health and medication use. Blood samples will be collected at study entry when enlisted for transplantation, at pre-defined intervals after transplantation, and if primary infection with or reactivation of CMV or VZV occurs during follow-up. Health data will be collected from hospital records and national registries.
Blood samples will be separated into peripheral blood mononuclear cells (PBMC) and plasma and stored in a biobank for analysis of PBMC phenotype and function, concentrations of inflammatory markers and mediators, CMV and VZV viral load and serology and other in-depth immunological analyses. Analyses will be performed at the Technical University of Denmark.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet
- •Aged 18 years or older
排除标准
- •Inability to understand the study information
研究组 & 干预措施
Liver transplant recipients
All adults enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet (N = around 60 per year) will be invited to participate regardless of indication for liver transplantation. These participants are expected to undergo a liver transplantation and will continue in the study after the procedure.
结局指标
主要结局
Frequency, phenotype and function of CMV- and VZV-specific T cells (descriptive)
时间窗: 1.5 years
Including: TCR clonotypes, cell surface markers and cytokine profile of T cell populations specific towards immunodominant CMV and VZV epitopes.
次要结局
- Primary CMV infection(10 years)
- VZV reactivation(10 years)
- CMV reactivation(10 years)
研究者
Susanne Dam Nielsen, MD, DMSc
Professor
Rigshospitalet, Denmark