What is the management of high titre Epstein-Barr Virus (EBV) viraemia in patients with Graft-Versus-Host Disease (GVHD) after solid liver organ transplantation?

From the Guidelines

The management of high titre EBV viraemia in patients with Graft-Versus-Host Disease (GVHD) after solid liver organ transplantation primarily involves reducing immunosuppressive therapy when possible, to allow the patient's immune system to control EBV replication. This approach is crucial as it directly addresses the root cause of the increased susceptibility to EBV viraemia, which is the immunosuppressed state of the patient. According to the EASL clinical practice guidelines on liver transplantation 1, patients with EBV seropositivity before liver transplantation and those treated with aggressive immunosuppressive regimens are at a higher risk of developing post-transplant lymphoproliferative disorders (PTLD). Key considerations in managing these patients include:

• Reducing immunosuppressive therapy as the first step, which may need to be balanced against the risk of graft rejection.
• Employing additional therapies such as rituximab, chemotherapy, radiation, and surgery if reduction in immunosuppression does not yield the desired response, as suggested by the guidelines 1.
• Regular monitoring of EBV viral load to assess treatment response and adjust the management plan accordingly.
• Considering the use of antiviral medications, though their efficacy against EBV is limited, and other supportive measures like IVIG for passive immunity. The goal of these management strategies is to prevent the progression to PTLD, a serious complication that can arise from unchecked EBV proliferation in immunosuppressed patients.

From the Research

Management of High Titre EBV Viraemia in Patients with GVHD

The management of high titre Epstein-Barr Virus (EBV) viraemia in patients with Graft-Versus-Host Disease (GVHD) after solid liver organ transplantation is a complex issue.

• The treatment approaches for GVHD after liver transplantation have been varied, with some studies suggesting the use of high-dose steroids, calcineurin inhibitors, and other immunosuppressive agents 2.
• However, the mortality rate with these treatments has been high, ranging from 73% to 100% 2.
• Some studies have reported success with the use of CD2-blockers and TNF-α antagonists, with a lower mortality rate of 25% 2.
• The diagnosis of GVHD is typically made based on clinical and histologic evidence, supported by chimerism studies showing donor HLA alleles in the recipient bone marrow or blood 3.
• The clinical features of GVHD after liver transplantation include skin rash, pancytopenia, and diarrhea, with a median time to onset of 28 days 2.

Treatment Approaches

• Reduction of immunosuppression has been proposed as a novel therapeutic approach, allowing the patient's immune system to reject the allograft donor T cells 4.
• This approach has been shown to be effective in some cases, with rapid loss of donor T cell chimerism and resolution of symptoms 4.
• However, the results have been variable, and larger studies are needed to further evaluate this approach 4.
• Corticosteroids, such as methylprednisolone, have been used to treat GVHD after liver transplantation, with some patients responding well to treatment 5.
• The use of G-CSF and GM-CSF has also been reported, although the effectiveness of these treatments is unclear 5.

Risk Factors and Outcomes

• Recipient age over 50 years has been identified as a risk factor for GVHD after liver transplantation 2.
• Hepatocellular carcinoma has been overrepresented in reported cases of GVHD after liver transplantation, while chronic hepatitis C has been underrepresented 2.
• The mortality rate with GVHD after liver transplantation is high, with sepsis being the most common cause of death 2.