By Joseph F. John, MD, FACP, FIDSA, FSHEA
Clinical Professor of Medicine and Microbiology, Medical University of South Carolina and Lowcountry Infectious Diseases, Charleston
SYNOPSIS: Cytomegalovirus (CMV) viremia emerges in the majority of CMV seronegative recipients of liver transplants from CMV seropositive donors, most often within the first post-transplant month. The only independent risk factor identified was increasing donor age.
SOURCE: Singh N, Winston DJ, Razonable RR, et al. Risk factors for cytomegalovirus viremia following liver transplantation with a seropositive donor and seronegative recipient receiving antiviral therapy. J Infect Dis 2021;223:1073-1077.
Singh and colleagues previously reported a randomized controlled trial in cytomegalovirus (CMV) seronegative patients who received liver transplants from seropositive donors (D+R-) that found that the use of preemptive valganciclovir was associated with fewer episodes of CMV disease when compared to its prophylactic administration.1 The trigger for initiation of preemptive valganciclovir was the occurrence of CMV viremia at any level as detected with a sensitive polymerase chain reaction (PCR). Now the same group has published a post hoc analysis evaluating the risk factors for the occurrence of that viremia in those assigned to preemptive therapy.
The final analysis included 94 patients who had weekly tests for CMV viremia totaling 1,197 blood samples. Of these, 79 (84%) developed viremia during the 100 days after transplantation, with a mean interval of 24.5 days to the first positive result. The cumulative incidences of viremia among these 79 patients were 20%, 44%, and 70% by two, three, and four weeks, respectively. The only factor identified as an independent risk factor for the development of viremia was greater donor age, with an odds ratio of 2.20 for each quartile increase in donor age (95% confidence interval [CI], 1.07 to 4.52; P = 0.031).
COMMENTARYThis study shows that CMV viremia is very common after transplantation of a CMV-positive liver into a CMV-negative recipient. The value of the study is to alert clinicians that a CMV syndrome could occur as early as two weeks from infection propagated by a CMV-positive donor and will be detected, on average, about three weeks after transplantation.
The study does not address the adverse effects of new infection in recipients, but it did find that the rates of rejection were no higher in recipients with viremia than those without viremia. The authors suggested that immune senescence is responsible for the higher rates of viremia in older patients, as noted in earlier studies of healthy seropositive patients. What is not known, as stressed by the authors, is what variables in donors may contribute to the rate of viremia in recipients — a facet that should be studied further.
Dr. Nina Singh in Pittsburgh has a long and illustrious career in transplant infectious diseases. Along with her multicenter colleagues, she again has opened a window of opportunity with this observation in liver transplantation. This study was conducted with National Institute of Allergy and Infectious Diseases/National Institutes of Health oversight and can be found at ClinicalTrials.gov, registration number NCT01552369.
REFERENCE
- Singh N, Winston DJ, Razonable RR, et al. Effect of preemptive therapy vs antiviral prophylaxis on cytomegalovirus disease in seronegative liver transplant recipients with seropositive donors: A randomized clinical trial. JAMA 2020;323:1378-1387.
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