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Effectiveness of Preemptive Therapy for Cytomegalovirus Disease in Pediatric Liver Transplantation

Nicastro, Emanuele MD, PhD; Giovannozzi, Sara MLS; Stroppa, Paola MD; Casotti, Valeria MD; Callegaro, Anna Paola MD; Tebaldi, Alessandra MD; Farina, Claudio MD; Colledan, Michele MD, FEBS; D'Antiga, Lorenzo MD, FEBT

doi: 10.1097/TP.0000000000001531
Original Clinical Science-Liver

Background: Most pediatric liver transplantation (LT) centers administer long courses of prophylaxis against cytomegalovirus (CMV) without evidence of benefit and with significant drug exposure and costs. We aimed at evaluating overall outcomes, direct and putative indirect effects of CMV, possible impact of viremia and risk factors for CMV infection in pediatric LT recipients managed with ganciclovir-based preemptive therapy (PET).

Methods: The records of all the children who underwent LT between 2008 and 2014 were retrospectively analyzed.

Results: One hundred children were included. Three children had CMV disease; no CMV-related death or graft loss was recorded. The only identified risk factor for CMV infection was the donor/recipient serostatus (odds ratio, 17.23; 95% confidence interval, 1.88-157.87; P = 0.012), while viremia per se did not worsen LT outcomes, such as the incidence of acute rejection, Epstein-Barr virus infection, sepsis, biliary and vascular complications, nor graft dysfunction/loss or death at 3 and 5 years after LT. When compared with a historical cohort of children receiving ganciclovir prophylaxis, PET did not differ from prophylaxis for any of the selected outcomes, but was rather associated with lower antiviral drug exposure (6.4 ± 13 days vs 38.6 ± 14 days, P < 0.0001) and cost per patient (2.2 ± 3.9 k€ vs 6.6 ± 8.2 k€, P = 0.001).

Conclusions: PET is effective in controlling CMV in children receiving LT, with lower costs and lower exposure to antivirals.

In liver transplantation (LT), preemptive CMV therapy (PET) has proven comparable to universal prophylaxis (UP) in controlling incidence of CMV disease, acute rejection and overall mortality in adults but data are less convincing in children. These authors provide evidence that PET is valuable, drug-sparing and cost-effective and should be preferred to UP in children undergoing LT in settings where viral monitoring is available.

1 Pediatric Gastroenterology, Hepatology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy.

2 Microbiology and Virology, Hospital Papa Giovanni XXIII, Bergamo, Italy.

3 Infectious Diseases, Hospital Papa Giovanni XXIII, Bergamo, Italy.

4 General and Transplant Surgery, Hospital Papa Giovanni XXIII, Bergamo, Italy.

Received 22 April 2016. Revision received 27 August 2016.

Accepted 23 September 2016.

The authors declare no funding or conflicts of interest.

E.N. participated in the study conception and design, acquisition of data, analysis and interpretation of data, drafting of article. S.G. participated in the acquisition of data. P.S. participated in the analysis and interpretation of data and critical revision. A.P.C. participated in the analysis and interpretation of data. A.T. participated in the analysis and interpretation of data and critical revision. C.F. participated in the critical revision. M.C. participated in the analysis and interpretation of data and critical revision. L.D.A. participated in the study conception and design, analysis and interpretation of data, and critical revision.

Correspondence: Lorenzo D'Antiga, MD, FEBT, Hospital Papa Giovanni XXIII, Piazza OMS, 1, 24127, Bergamo, Italy. (ldantiga@asst-pg23.it).

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