{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:58:17Z","timestamp":1792979897879,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["2023A18"],"award-info":[{"award-number":["2023A18"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transplant Infectious Dis"],"published-print":{"date-parts":[[2025,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Cytomegalovirus (CMV) infection in pediatric liver transplant recipients is a major concern. Ganciclovir (GCV) and valganciclovir (VGCV) are the first\u2010line treatment agents; however, neutropenia is a common adverse effect.\n Nucleoside diphosphate\u2010linked moiety X\u2010type motif 15<\/jats:italic>\n (\n NUDT15<\/jats:italic>\n ) variants are linked to thiopurine\u2010induced myelosuppression; however, their associations with GCV\/VGCV\u2010induced cytotoxicity remain unclear. We aimed to examine the association between loss\u2010of\u2010function variants of the\n NUDT15<\/jats:italic>\n genotype and drug\u2010related adverse reactions in pediatric transplant recipients, specifically liver transplant recipients, treated with GCV\/VGCV.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We retrospectively analyzed data from pediatric liver transplant recipients treated with GCV\/VGCV for CMV disease or infection between 2012 and 2022. Patients were genotyped for\n NUDT15<\/jats:italic>\n R139C, R139H, and V18I variants, and hematological outcomes were compared between the normal and variant groups.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 40 patients, 10 (25%) harbored\n NUDT15<\/jats:italic>\n variants. The incidence rate of neutropenia (60% vs. 7%;\n p<\/jats:italic>\n < 0.01) and percentage decrease in neutrophil count (\u221265.1% vs. \u221245.9%;\n p<\/jats:italic>\n = 0.02) were significantly higher in the variant group than in the normal group. No significant differences were observed in the incidence of leukopenia, anemia, thrombocytopenia, hepatic toxicity, or renal toxicity.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n NUDT15<\/jats:italic>\n variants were associated with an increased risk of neutropenia in pediatric liver transplant recipients receiving GCV\/VGCV treatment. Genetic screening before treatment initiation may help optimize antiviral therapy, minimize hematological toxicity, and improve patient management. Further studies are needed to refine the treatment strategies.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/tid.70079","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:26:33Z","timestamp":1753806393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Associations of\n Nucleoside Diphosphate\u2010Linked Moiety X\u2010Type Motif 15<\/i>\n Variants With Neutropenia During Antiviral Therapy for Cytomegalovirus Disease in Pediatric Liver Transplant Recipients"],"prefix":"10.1111","volume":"27","author":[{"given":"Ken\u2010ichi","family":"Iwata","sequence":"first","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Torii","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Haruta","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Transplantation Surgery Nagoya University Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010ichi","family":"Kawada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Fields Virology","author":"Howley P. 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