Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study

NCT05532540 | Active Not Recruiting

• 2 other identifiers: H-220392260073947
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Cytomegalovirus Infections; Varicella Zoster Virus Infection; Liver Transplant; Complications

Keywords

Cytomegalovirus; Herpesvirus 3, Human; Liver Transplantation; T-Lymphocytes; Inflammation; Immunodominant Epitopes; Major Histocompatibility Complex

Outcome Measures

Primary Outcomes (1)

• Frequency, phenotype and function of CMV- and VZV-specific T cells (descriptive)

  Including: TCR clonotypes, cell surface markers and cytokine profile of T cell populations specific towards immunodominant CMV and VZV epitopes.

  1.5 years

Secondary Outcomes (3)

• Primary CMV infection

  10 years

• VZV reactivation

  10 years

• CMV reactivation

  10 years

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All adults enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet (N = around 60 per year) will be invited to participate.

You may qualify if:

• Enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet
• Aged 18 years or older

You may not qualify if:

• Inability to understand the study information

Sponsors & Collaborators

• Susanne Dam Nielsen, MD, DMSc: lead
• Technical University of Denmark: collaborator
• Rigshospitalet, Denmark: collaborator

Study Sites (3)

Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

Copenhagen, 2100, Denmark

Location

Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet

Copenhagen, 2100, Denmark

Location

Department of Health Technology, Technical University of Denmark

Lyngby, 2800, Denmark

Location

Related Publications (1)

• Suarez-Zdunek MA, Saini SK, Pedersen CR, Hamm SR, Hald A, Rasmussen A, Hillingso JG, Hadrup SR, Nielsen SD. Herpesvirus immunology in solid organ transplant recipients - liver transplant study (HISTORY): a retrospective and prospective observational cohort study. BMC Infect Dis. 2023 Apr 6;23(1):214. doi: 10.1186/s12879-023-08153-8.

  PMID: 37024811 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood will be collected and separated into peripheral blood mononuclear cells (PBMC) and plasma, both of which are stored in a biobank.

MeSH Terms

Conditions

Cytomegalovirus Infections; Varicella Zoster Virus Infection; Chickenpox; Inflammation

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Susanne D Nielsen, Professor, MD, DMSc

  Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

  PRINCIPAL INVESTIGATOR

• Sine R Hadrup, Professor, MSc, PhD

  Department of Health Technology, Technical University of Denmark

  PRINCIPAL INVESTIGATOR

• Moises Alberto Suarez Zdunek, MD

  Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

  STUDY DIRECTOR

• Sebastian R Hamm, BSc

  Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

  STUDY DIRECTOR

• Annemette Hald, RN

  Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

  STUDY DIRECTOR

• Sunil K Saini, MSc, PhD

  Department of Health Technology, Technical University of Denmark

  STUDY DIRECTOR

• Allan Rasmussen, MD

  Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet

  STUDY DIRECTOR

• Jens G Hillingsø, MD, PhD

  Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet

  STUDY DIRECTOR

• Christian R Pedersen, MD

  Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 3, 2022
• First Posted: September 8, 2022
• Study Start: January 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2033
• Last Updated: April 3, 2025

Record last verified: 2025-04

Locations

DK (3)