{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:20:25Z","timestamp":1791937225581,"version":"4.3.4"},"reference-count":65,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pediatric hepatocellular carcinoma (HCC) is a rare malignant liver tumor affecting children and adolescents and occurring either sporadically or in the context of underlying liver disease. In this review, we detail the epidemiology of pediatric HCC with a focus on predisposing factors including hepatic or systemic disease, genetic disorders, and familial cancer syndromes. We summarize existing research on the pathophysiology of pediatric HCC, including molecular mechanisms of oncogenesis, highlighting unique disease features differentiating pediatric HCC from adult HCC. We then survey the landscape of therapeutic options for pediatric HCC, including novel therapeutics. Lastly, we discuss the pathologic spectrum upon which pediatric HCC is postulated to exist, ranging from hepatoblastoma to HCC and including the hybrid entity hepatocellular neoplasm not otherwise specifed (HCN-NOS). In summary, we highlight the key clinical and molecular features of pediatric HCC that may inform future research and novel approaches to the clinical care of these patients.<\/jats:p>","DOI":"10.3390\/ijms26031252","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T08:05:41Z","timestamp":1738310741000},"page":"1252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pediatric Hepatocellular Carcinoma: A Review of Predisposing Conditions, Molecular Mechanisms, and Clinical Considerations"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3953-8273","authenticated-orcid":false,"given":"Elizabeth P.","family":"Young","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Oncology, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8957-3870","authenticated-orcid":false,"given":"Allison F.","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun A.","family":"Rangaswami","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Oncology, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1097\/MPG.0000000000002285","article-title":"Predisposing conditions to pediatric hepatocellular carcinoma and association with outcomes: Single-center experience","volume":"68","author":"Cowell","year":"2019","journal-title":"J. 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