{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:01:57Z","timestamp":1790776917816,"version":"4.1.0"},"reference-count":26,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:p>We report a case of delayed acute liver injury (ALI) after treatment with delandistrogene moxeparvovec-rokl (DM), an adeno-associated virus\u2013based gene therapy, in a 10-year-old ambulatory boy with Duchenne muscular dystrophy (DMD). The patient had a duplication of exons 8\u201311 in the DMD gene and was on chronic prednisone. He received prophylactic oral prednisone (1\u00a0mg\/kg\/d) starting 1\u00a0day before DM infusion. Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK) levels were elevated, consistent with DMD. On day 34 after infusion, ALT and AST began to rise without gamma-glutamyl transpeptidase (GGT) elevation. By day 41, transaminases were more than 7\u00d7\u2009baseline with elevated GGT and bilirubin, prompting hospitalization. He was treated with intravenous methylprednisolone, increased oral prednisone, and sirolimus. Liver enzymes rapidly improved and returned to baseline by day 69.<\/jats:p>\n                  <jats:p>Immunologic studies revealed CD8+ T-cell activation and innate immune activation via mildly elevated IL-18 that normalized without additional immunosuppression. The patient remained clinically stable. Infectious workup, liver ultrasonogram, and coagulation studies were unremarkable. Notably, the ALT\/CK ratio increased more than 10-fold 1\u00a0 week before GGT elevation and before ALT exceeded the 95% CI predicted by a CK- and age-adjusted model, suggesting its potential as an early biomarker of liver injury in DMD.<\/jats:p>\n                  <jats:p>This case highlights the challenges of interpreting liver enzymes in DMD, the potential utility of the ALT\/CK ratio for early detection of ALI, and the role of immunophenotyping in guiding immunosuppressive therapy. Early recognition and timely escalation, including use of sirolimus, may help mitigate serious liver toxicity after gene therapy.<\/jats:p>","DOI":"10.1542\/peds.2025-074192","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:03:08Z","timestamp":1770854588000},"source":"Crossref","is-referenced-by-count":2,"title":["ALT\/CK Ratio as an Early Marker of Liver Injury After Gene Therapy in Duchenne Muscular Dystrophy"],"prefix":"10.1542","volume":"157","author":[{"given":"Eleni","family":"Drakou","sequence":"first","affiliation":[{"name":"1Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catrice","family":"Needum","sequence":"additional","affiliation":[{"name":"2Gene Therapy Center of Excellence, Nationwide Children\u2019s Hospital, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylee","family":"Konst","sequence":"additional","affiliation":[{"name":"2Gene Therapy Center of Excellence, Nationwide Children\u2019s Hospital, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Chagat","sequence":"additional","affiliation":[{"name":"2Gene Therapy Center of Excellence, Nationwide Children\u2019s Hospital, Columbus, Ohio"},{"name":"3Division of Neurology, Nationwide Children\u2019s Hospital, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshini S.","family":"Abraham","sequence":"additional","affiliation":[{"name":"4Department of Pathology and Laboratory Medicine, Nationwide Children\u2019s Hospital, Columbus, Ohio"},{"name":"5Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Weymann","sequence":"additional","affiliation":[{"name":"6Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children\u2019s Hospital, Columbus, Ohio"},{"name":"7Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Flanigan","sequence":"additional","affiliation":[{"name":"1Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, Ohio"},{"name":"2Gene Therapy Center of Excellence, Nationwide Children\u2019s Hospital, Columbus, Ohio"},{"name":"3Division of Neurology, Nationwide Children\u2019s Hospital, Columbus, Ohio"},{"name":"7Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio"},{"name":"8Department of Neurology, The Ohio State University College of Medicine, Columbus, 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