{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T23:22:15Z","timestamp":1781911335414,"version":"3.54.5"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Transplantation"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary tyrosinemia type 1 is a rare metabolic condition associated with an increased risk of hepatocellular carcinoma. Nitisinone (2\u2010[2\u2010nitro\u20104\u2010trifluoromethylbenzoyl]\u20101,3\u2010cyclohexanedione, <jats:styled-content style=\"fixed-case\">NTBC<\/jats:styled-content>) treatment has reduced but not eliminated the risk. The delayed initiation of nitisinone treatment, and persistently abnormal \u03b11\u2010fetoprotein (<jats:styled-content style=\"fixed-case\">AFP<\/jats:styled-content>) levels are recognized to be risk factors for late\u2010onset hepatocellular carcinoma. We report three children diagnosed and treated with nitisinone since infancy who developed hepatocellular carcinoma despite long\u2010term normalization of <jats:styled-content style=\"fixed-case\">AFP.<\/jats:styled-content><\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective review of all patients with tyrosinemia on nitisinone managed at our center was undertaken. Patient demographics, age at diagnosis, duration of therapy, timing of AFP normalization, and radiographic imaging findings were noted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three patients at our center with tyrosinemia type 1 developed hepatocellular carcinoma 9\u201313\u2009years after diagnosis despite long\u2010term nitisinone therapy and normalization of AFP. Two patients developed new nodules on imaging with an elevation of AFP leading to the diagnosis and subsequent liver transplant. The third patient proceeded with liver transplant because of a very nodular liver and increasing splenomegaly despite normal AFP and no change in surveillance gadoxetate magnetic resonance imaging. Early hepatocellular carcinoma was found in her liver explant. All three patients were cirrhotic at diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients with hereditary tyrosinemia type 1, especially those already cirrhotic at diagnosis, remain at high risk of developing hepatocellular carcinoma despite long\u2010term nitisinone therapy and AFP normalization, and warrant close monitoring and surveillance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/petr.14334","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T03:59:21Z","timestamp":1655179161000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hepatocellular carcinoma requiring liver transplantation in hereditary tyrosinemia type 1 despite nitisinone therapy and \u03b11\u2010fetoprotein normalization"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8842-9546","authenticated-orcid":false,"given":"Shreya","family":"Bhushan","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Liver Transplantation Queensland Children's Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlton","family":"Noble","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Liver Transplantation Queensland Children's Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariha","family":"Balouch","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Liver Transplantation Queensland Children's Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lewindon","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Liver Transplantation Queensland Children's Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Lampe","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Central Laboratory Pathology Queensland  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hodgkinson","sequence":"additional","affiliation":[{"name":"Queensland Liver Transplant Service, Princess Alexandra Hospital and Queensland Children's Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"McGill","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Central Laboratory Pathology Queensland  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Looi","family":"Ee","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Liver Transplantation Queensland Children's Hospital  Brisbane Queensland 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