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      Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients

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          Abstract

          Background

          Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation.

          Methods

          A retrospective study of 58 children aged 1–17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log 10 Geq/ml in > 50% of the samples during ≥ 6 months.

          Results

          At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5–6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7–13).

          Conclusions

          CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.

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          Most cited references49

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          Epstein-Barr virus: exploiting the immune system.

          In vitro, Epstein-Barr virus (EBV) will infect any resting B cell, driving it out of the resting state to become an activated proliferating lymphoblast. Paradoxically, EBV persists in vivo in a quiescent state in resting memory B cells that circulate in the peripheral blood. How does the virus get there, and with such specificity for the memory compartment? An explanation comes from the idea that two genes encoded by the virus--LMP1 and LMP2A--allow EBV to exploit the normal pathways of B-cell differentiation so that the EBV-infected B blast can become a resting memory cell.
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            Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients.

            We compared the efficacy and safety of valganciclovir with those of oral ganciclovir in preventing cytomegalovirus (CMV) disease in high-risk seronegative solid organ transplant (SOT) recipients of organs from seropositive donors (D+/R-). In this randomised, prospective, double-blind, double-dummy study, 364 CMV D+/R- patients received valganciclovir 900 mg once daily or oral ganciclovir 1000 mg three times a day (tid) within 10 days of transplant and continued through 100 days. CMV disease, plasma viremia, acute graft rejection, graft loss and safety were analyzed up to 6 and 12 months post-transplant. Endpoint committee-defined CMV disease developed in 12.1% and 15.2% of valganciclovir and ganciclovir patients, respectively, by 6 months, though with a difference in the relative efficacy of valganciclovir and ganciclovir between organs (i.e. an organ type-treatment interaction). By 12 months, respective incidences were 17.2% and 18.4%, and the incidence of investigator-treated CMV disease events was comparable in the valganciclovir (30.5%) and ganciclovir (28.0%) arms. CMV viremia during prophylaxis was significantly lower with valganciclovir (2.9% vs. 10.4%; p=0.001), but was comparable by 12 months (48.5% valganciclovir vs 48.8% ganciclovir). Time-to-onset of CMV disease and to viremia were delayed with valganciclovir; rates of acute allograft rejection were generally lower with valganciclovir. Except for a higher incidence of neutropenia with valganciclovir (8.2%, vs 3.2% ganciclovir) the safety profile was similar for both drugs. Overall, once-daily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients.
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              Post-Transplantation Lymphoproliferative Disorders in Adults

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                Author and article information

                Contributors
                jenny.lindahl@vgregion.se
                Journal
                Pediatr Nephrol
                Pediatr. Nephrol
                Pediatric Nephrology (Berlin, Germany)
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0931-041X
                1432-198X
                4 December 2019
                4 December 2019
                2020
                : 35
                : 3
                : 427-439
                Affiliations
                [1 ]GRID grid.1649.a, ISNI 000000009445082X, Department of Pediatrics, Queen Silvia Children’s Hospital, , Sahlgrenska University Hospital, ; Region Västra Götaland, Gothenburg, Sweden
                [2 ]GRID grid.8761.8, ISNI 0000 0000 9919 9582, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, , University of Gothenburg, ; Gothenburg, Sweden
                [3 ]GRID grid.1649.a, ISNI 000000009445082X, Department of Infectious Diseases, , Sahlgrenska University Hospital, ; Region Västra Götaland, SE-416 85 Gothenburg, Sweden
                [4 ]GRID grid.8761.8, ISNI 0000 0000 9919 9582, Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, , University of Gothenburg, ; Gothenburg, Sweden
                [5 ]GRID grid.1649.a, ISNI 000000009445082X, Department of Clinical Microbiology, , Sahlgrenska University Hospital, ; Region Västra Götaland, Gothenburg, Sweden
                Author information
                http://orcid.org/0000-0001-8641-7402
                Article
                4401
                10.1007/s00467-019-04401-9
                6969008
                31802220
                611fc32d-2b47-4287-9f11-e56137338a70
                © The Author(s) 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 6 August 2019
                : 22 September 2019
                : 14 October 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100011675, Göteborgs Frimurares;
                Funded by: FundRef http://dx.doi.org/10.13039/501100005689, Göteborgs Läkaresällskap;
                Funded by: Märta och Gustaf Ågrens Stiftelse (SE)
                Funded by: Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement
                Award ID: ALF GBG-74040, 71550, 70450, 70150, 73740
                Categories
                Original Article
                Custom metadata
                © IPNA 2020

                Nephrology
                epstein-barr virus. ebv dna,chronic high load carrier,infection. pediatric,renal transplantation

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