{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:07:01Z","timestamp":1789175221297,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"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","award":["JP22fk0108541"],"award-info":[{"award-number":["JP22fk0108541"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hepatotoxicity is a common and significant adverse effect associated with adeno\u2010associated virus (AAV) gene therapy; however, the underlying mechanisms remain unknown. In this study, we demonstrated innate immune activation in two patients with spinal muscular atrophy shortly after receiving AAV9 gene therapy with onasemnogene abeparvovec. Both patients developed marked hyperferritinemia accompanied by hepatotoxicity, thrombocytopenia, hypertriglyceridemia, and hypofibrinogenemia, all of which are the diagnostic criteria for macrophage activation syndrome. To evaluate their immune responses, serial analyses of serum cytokines\/chemokines and flow cytometry were performed. Surges in macrophage\u2010associated cytokine levels were observed in proportion to the severity of adverse events within 1\u2009week after AAV vector infusion, suggesting that macrophage activation contributed to the pathogenesis of these adverse effects. Our findings clarify the immunological basis underlying hepatotoxicity in patients after AAV gene therapy. Furthermore, these findings provide a rationale for using various immunosuppressants or chemokine blockers in patients exhibiting severe adverse effects.<\/jats:p>","DOI":"10.1111\/liv.70760","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T07:57:18Z","timestamp":1783151838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adeno\u2010Associated Virus Gene Therapy for Spinal Muscular Atrophy Induces Hepatotoxicity via Cytokine and Macrophage Activation"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2762-0205","authenticated-orcid":false,"given":"Aiko","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Viral Pathogenesis and Controls National Institute of Global Health and Medicine, Japan Institute for Health Security  Ichikawa Chiba Japan"},{"name":"Department of Pediatrics Ibaraki Children's Hospital  Mito Ibaraki 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