Management of cytomegalovirus infection and disease in liver transplant recipients

Abstract

Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation.

Risk factors for cytomegalovirus reactivation after liver transplantation: Can pre‐transplant cytomegalovirus antibody titers predict outcome?

“…8,25 Overimmunosuppression is a well-known risk factor for CMV and other opportunistic infections after transplantation. 3 Induction therapy with IL2RA, a chimeric monoclonal antibody, has been believed to cause a lower incidence of infection in comparison with induction therapy with polyclonal antibodies. A recent meta-analysis found that CMV infection was not increased or was even lower in LT recipients who received IL2RA induction versus corticosteroid induction.…”

“…2 In comparison with the high-risk status of CMV-seronegative recipients of organs from CMVseropositive donors, CMV-seropositive SOT recipients are considered only at modest risk for CMV infection after liver transplantation (LT), with rates ranging from 8% to 19%. 3 The preexisting CMV-specific immunity among CMV-seropositive donors appears to mitigate viral replication kinetics and its clinical outcome. Accordingly, management guidelines suggest that CMV monitoring and preemptive therapy may be a reasonable option for the prevention of CMV disease in CMV-seropositive LT recipients.…”

“…Accordingly, management guidelines suggest that CMV monitoring and preemptive therapy may be a reasonable option for the prevention of CMV disease in CMV-seropositive LT recipients. 2,4 Despite pre-existing immunity, CMV reactivation remains to occur in CMV83 seropositive LT patients (3). Several risk factors for CMV reactivation in CMVseropositive SOT recipients, including augmented immunosuppression (leading to suppression of CMVspecific immunity) have been described.…”

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

“…Important developments have since changed the perspectives of CMV infection, like assessment of specific donor (D)/recipient (R) risk constellations and the introduction of potent antiviral drugs (ganciclovir; valganciclovir). Between 1% and 30% of liver transplant patients are supposed to develop CMV disease in the absence of preventive strategies [115,116] . Indirect virus efficacies were demonstrated to account essentially for CMV-related morbidity and mortality [115,116] .…”

“…Between 1% and 30% of liver transplant patients are supposed to develop CMV disease in the absence of preventive strategies [115,116] . Indirect virus efficacies were demonstrated to account essentially for CMV-related morbidity and mortality [115,116] . These are mainly triggered by the capability of CMV to adversely modulate the recipients' immune system.…”