Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

Hepatoblastoma

Nature Reviews Disease Primers volume 11, Article number: 36 (2025) Cite this article

Subjects

Abstract

Hepatoblastoma is the most common primary liver cancer in children, with an incidence of approximately 1.5 cases per million children per year. Most cases are sporadic, typically presenting at a median age of 18 months, with only 5% occurring after 4 years of age. Clinical presentation often includes an abdominal mass and, less commonly, abdominal pain, weight loss, jaundice and precocious puberty. Low birth weight is a significant risk factor, along with genetic conditions such as Beckwith–Wiedemann syndrome, Simpson–Golabi–Behmel syndrome, familial adenomatous polyposis and trisomy 18. Screening protocols for hepatoblastoma are recommended for children with predisposing conditions. Medical imaging is crucial for hepatoblastoma diagnosis and staging, with abdominal ultrasonography being the initial modality of choice, followed by abdominal contrast MRI for detailed evaluation and monitoring. Chest computer tomography is indicated to evaluate potential lung metastases. The Pretreatment Extent of Disease (PRETEXT) system is employed for hepatoblastoma staging and for guiding treatment strategies such as surgical resection and chemotherapy. Patients with advanced hepatoblastoma may require liver transplantation. Advancements in surgery and chemotherapy have improved survival rates, with 5-year survival rates exceeding 80–90% in localized disease. However, challenges remain in treating individuals with high-risk and metastatic hepatoblastoma. Ongoing research into treatment stratification, the introduction of novel therapies, including targeted and immune therapies, and the application of otoprotectants are essential to address refractory or recurrent hepatoblastoma and to increase the overall survival of patients. Long-term quality of life and the management of treatment-related sequelae are becoming increasingly important as survival rates improve.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: PRETEXT classification.
Fig. 2: Characterization of hepatoblastoma and HCC via molecular aberrations and cell of origin.
Fig. 3: Scheme of biological mechanisms involved in hepatoblastoma development.
Fig. 4: Hepatoblastoma MRI.
Fig. 5: Hepatoblastoma pathology.
Fig. 6: Liver segmental anatomy and types of surgical liver resection.

Similar content being viewed by others

References

  1. Spector, L. G. & Birch, J. The epidemiology of hepatoblastoma. Pediatr. Blood Cancer 59, 776–779 (2012).

    Article  PubMed  Google Scholar 

  2. Meyers, R., Hiyama, E., Czauderna, P. & Tiao, G. M. Liver tumors in pediatric patients. Surg. Oncol. Clin. North Am. 30, 253–274 (2021).

    Article  Google Scholar 

  3. Srinivasan, S. et al. Treatment outcomes and prognostic factors in children with hepatoblastoma using a risk-stratified approach. Pediatr. Blood Cancer 70, e30302 (2023).

    Article  CAS  PubMed  Google Scholar 

  4. Czauderna, P. et al. The Children’s Hepatic Tumors International Collaboration (CHIC): novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model. Eur. J. Cancer 52, 92–101 (2016).

    Article  PubMed  Google Scholar 

  5. Clavería-Cabello, A. et al. Identification and experimental validation of druggable epigenetic targets in hepatoblastoma. J. Hepatol. 79, 989–1005 (2023).

    Article  PubMed  Google Scholar 

  6. Espinoza, A. F. et al. A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma. J. Hepatol. 80, 610–621 (2024).

    Article  CAS  PubMed  Google Scholar 

  7. Kim, S. Y. et al. Genomic profiles of a hepatoblastoma from a patient with Beckwith-Wiedemann syndrome with uniparental disomy on chromosome 11p15 and germline mutation of APC and PALB2. Oncotarget 8, 91950–91957 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hirschman, B. A., Pollock, B. H. & Tomlinson, G. E. The spectrum of APC mutations in children with hepatoblastoma from familial adenomatous polyposis kindreds. J. Pediatr. 147, 263–266 (2005).

    Article  CAS  PubMed  Google Scholar 

  9. Pereira, E. M. et al. Hepatoblastoma in a mosaic trisomy 18 patient. J. Pediatr. Hematol. Oncol. 34, e145–e148 (2012).

    Article  PubMed  Google Scholar 

  10. Aguiar, T. et al. Unraveling the genetic architecture of hepatoblastoma risk: birth defects and increased burden of germline damaging variants in gastrointestinal/renal cancer predisposition and DNA repair genes. Front. Genet. 13, 858396 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. DeBaun, M. R. & Tucker, M. A. Risk of cancer during the first four years of life in children from the Beckwith-Wiedemann syndrome registry. J. Pediatr. 132, 398–400 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. Eggermann, T., Maher, E. R., Kratz, C. P. & Prawitt, D. Molecular basis of Beckwith–Wiedemann syndrome spectrum with associated tumors and consequences for clinical practice. Cancers 14, 3083 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nussbaumer, G. & Benesch, M. Hepatoblastoma in molecularly defined, congenital diseases. Am. J. Med. Genet. A 188, 2527–2535 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Giardiello, F. M. et al. Risk of hepatoblastoma in familial adenomatous polyposis. J. Pediatr. 119, 766–768 (1991).

    Article  CAS  PubMed  Google Scholar 

  15. Turcotte, L. M. et al. Neonatal medical exposures and characteristics of low birth weight hepatoblastoma cases: a report from the Children’s Oncology Group. Pediatr. Blood Cancer 61, 2018–2023 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Achatz, M. I. et al. Cancer screening recommendations and clinical management of inherited gastrointestinal cancer syndromes in childhood. Clin. Cancer Res. 23, e107–e114 (2017).

    Article  PubMed  Google Scholar 

  17. Gröbner, S. N. et al. The landscape of genomic alterations across childhood cancers. Nature 555, 321–327 (2018).

    Article  PubMed  Google Scholar 

  18. López-Terrada, D. et al. Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG Liver Tumors Symposium. Mod. Pathol. 27, 472–491 (2014).

    Article  PubMed  Google Scholar 

  19. Sumazin, P. et al. Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups. Hepatology 65, 104–121 (2017). This pivotal genomic classification of hepatoblastoma into three molecular subtypes (hepatocytic, liver progenitor and mesenchymal) revolutionized our understanding of tumour biology and provided a framework for personalized treatment approaches.

    Article  CAS  PubMed  Google Scholar 

  20. Meyers, R. L. et al. Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children’s Hepatic Tumors International Collaboration. Lancet Oncol. 18, 122–131 (2017). This landmark study established a unified global approach to hepatoblastoma risk stratification by integrating data from multiple international trials, fundamentally changing how treatment decisions are made.

    Article  PubMed  Google Scholar 

  21. Eichenmüller, M. et al. The genomic landscape of hepatoblastoma and their progenies with HCC-like features. J. Hepatol. 61, 1312–1320 (2014).

    Article  PubMed  Google Scholar 

  22. Mokkapati, S. et al. β-Catenin activation in a novel liver progenitor cell type is sufficient to cause hepatocellular carcinoma and hepatoblastoma. Cancer Res. 74, 4515–4525 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. López-Terrada, D. et al. Histologic subtypes of HB are characterized by differential canonical Wnt and Notch pathway activation in DLK+ precursors. Hum. Pathol. 40, 783–794 (2009).

    Article  PubMed  Google Scholar 

  24. Marini, K. D. et al. Mechanisms of Hedgehog signalling in cancer. Growth Factors 29, 221–234 (2011).

    Article  CAS  PubMed  Google Scholar 

  25. Li, H. et al. Deregulation of Hippo kinase signalling in human hepatic malignancies. Liver. Int. 32, 38–47 (2012).

    Article  PubMed  Google Scholar 

  26. Tao, J. et al. Activation of β-catenin and Yap1 in human HB and induction of hepatocarcinogenesis in mice. Gastroenterology 147, 690–701 (2014).

    Article  CAS  PubMed  Google Scholar 

  27. Mo, J. S., Park, H. W. & Guan, K. L. The Hippo signaling pathway in stem cell biology and cancer. EMBO Rep. 15, 642–656 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Moya, I. M. & Halder, G. Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine. Nat. Rev. Mol. Cell Biol. 20, 211–226 (2019).

    Article  CAS  PubMed  Google Scholar 

  29. Borja, N. A. et al. Coffin-Siris syndrome and cancer susceptibility. Genet. Med. Open 1, 100818 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhou, S. et al. Comparative clinicopathologic and genomic analysis of hepatocellular neoplasm, not otherwise specified, and hepatoblastoma. Mod. Pathol. 37, 100385 (2024).

    Article  CAS  PubMed  Google Scholar 

  31. Hiyama, E. et al. High expression of telomerase is an independent prognostic indicator of poor outcome in hepatoblastoma. Br. J. Cancer 91, 972–979 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shalaby, T., Hiyama, E. & Grotzer, M. A. Telomere maintenance as therapeutic target in embryonal tumours. Anti-Cancer Agents Med. Chem. 10, 196–212 (2010).

    Article  CAS  Google Scholar 

  33. Ueda, Y. et al. Wnt signaling and telomerase activation of hepatoblastoma: correlation with chemosensitivity and surgical resectability. J. Pediatr. Surg. 46, 2221–2227 (2011).

    Article  PubMed  Google Scholar 

  34. Chiarle, R. Solving the chromosome puzzle of aneuploidy in cancer. Genes Dev. 35, 1073–1075 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Moroz, V. et al. The paediatric hepatic international tumour trial (PHITT): clinical trial design in rare disease. Trials 16, P224 (2015).

    Article  PubMed Central  Google Scholar 

  36. Nagae, G. et al. Genetic and epigenetic basis of hepatoblastoma diversity. Nat. Commun. 12, 5423 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cairo, S. et al. Hepatic stem-like phenotype and interplay of Wnt/β-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell 14, 471–484 (2008).

    Article  CAS  PubMed  Google Scholar 

  38. Hooks, K. B. et al. New insights into diagnosis and therapeutic options for proliferative hepatoblastoma. Hepatology 68, 89–102 (2018).

    Article  CAS  PubMed  Google Scholar 

  39. Regel, I. et al. IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically silenced in vascular invasive and metastatic tumors. Mol. Cancer 11, 9 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rivas, M. et al. DNA methylation as a key epigenetic player for hepatoblastoma characterization. Clin. Res. Hepatol. Gastroenterol. 45, 101684 (2021).

    Article  CAS  PubMed  Google Scholar 

  41. Carrillo-Reixach, J. et al. Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications. J. Hepatol. 73, 328–341 (2020).

    Article  CAS  PubMed  Google Scholar 

  42. Quintero Escobar, M., Maschietto, M., Krepischi, A. C. V., Avramovic, N. & Tasic, L. Insights into the chemical biology of childhood embryonal solid tumors by NMR-based metabolomics. Biomolecules 9, 843 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Sumazin, P. et al. Hepatoblastomas with carcinoma features represent a biological spectrum of aggressive neoplasms in children and young adults. J. Hepatol. 77, 1026–1037 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bergman, D., Halje, M., Nordin, M. & Engström, W. Insulin-like growth factor 2 in development and disease: a mini-review. Gerontology 59, 240–249 (2013).

    Article  CAS  PubMed  Google Scholar 

  45. Venkatraman, A. et al. Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence. Nature 500, 345–349 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Vu, T. H. & Hoffman, A. R. Promoter-specific imprinting of the human insulin-like growth factor-II gene. Nature 371, 714–717 (1994).

    Article  CAS  PubMed  Google Scholar 

  47. Honda, S. et al. Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma. Br. J. Cancer 99, 1891–1899 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gray, S. G., Kytölä, S., Matsunaga, T., Larsson, C. & Ekström, T. J. Comparative genomic hybridization reveals population-based genetic alterations in hepatoblastomas. Br. J. Cancer 83, 1020–1025 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Buendia, M. A. Genetic alterations in hepatoblastoma and hepatocellular carcinoma: common and distinctive aspects. Med. Pediatr. Oncol. 39, 530–535 (2002).

    Article  PubMed  Google Scholar 

  50. Li, X. et al. Disrupted IGF2 promoter control by silencing of promoter P1 in human hepatocellular carcinoma. Cancer Res. 57, 2048–2054 (1997).

    CAS  PubMed  Google Scholar 

  51. Martinez-Quetglas, I. et al. IGF2 Is Up-regulated by epigenetic mechanisms in hepatocellular carcinomas and is an actionable oncogene product in experimental models. Gastroenterology 151, 1192–1205 (2016).

    Article  CAS  PubMed  Google Scholar 

  52. Hirsch, T. Z. et al. Integrated genomic analysis identifies driver genes and cisplatin-resistant progenitor phenotype in pediatric liver cancer. Cancer Discov. 11, 2524–2543 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Rovina, D. et al. Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients. Sci. Rep. 10, 8275 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bell, A. C. & Felsenfeld, G. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405, 482–485 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Hark, A. T. et al. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405, 486–489 (2000).

    Article  CAS  PubMed  Google Scholar 

  56. Steenman, M. J. et al. Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms’ tumour. Nat. Genet. 7, 433–439 (1994).

    Article  CAS  PubMed  Google Scholar 

  57. Ravenel, J. D. et al. Loss of imprinting of insulin-like growth factor-II (IGF2) gene in distinguishing specific biologic subtypes of Wilms tumor. J. Natl Cancer Inst. 93, 1698–1703 (2001).

    Article  CAS  PubMed  Google Scholar 

  58. Tan, T. et al. Association between lncRNA‐H19 polymorphisms and hepatoblastoma risk in an ethic Chinese population. J. Cell. Mol. Med. 25, 742–750 (2021).

    Article  CAS  PubMed  Google Scholar 

  59. Adam, M. P. et al. (eds) GeneReviews® (University of Washington, 1993).

  60. Sharma, U. et al. Long non-coding RNA TINCR as potential biomarker and therapeutic target for cancer. Life Sci. 257, 118035 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Dong, R. et al. Genome-wide analysis of long noncoding RNA (lncRNA) expression in hepatoblastoma tissues. PLoS ONE 9, e85599 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Dong, R. et al. Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma. Cell Death Dis. 7, e2278 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhang, W. et al. LncRNA MIR205HG accelerates cell proliferation, migration and invasion in hepatoblastoma through the activation of MAPK signaling pathway and PI3K/AKT signaling pathway. Biol. Direct 17, 2 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Jiang, W., Ou, Z.-L., Zhu, Q., Yao, Y.-B. & Zai, H.-Y. LncRNA OIP5-AS1 aggravates the stemness of hepatoblastoma through recruiting PTBP1 to increase the stability of β-catenin. Pathol. Res. Pract. 232, 153829 (2022).

    Article  CAS  PubMed  Google Scholar 

  65. Lecerf, C., Le Bourhis, X. & Adriaenssens, E. The long non-coding RNA H19: an active player with multiple facets to sustain the hallmarks of cancer. Cell. Mol. Life Sci. 76, 4673–4687 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ecevit, Ç. Ö. et al. MicroRNA-17, MicroRNA-19b, MicroRNA-146a, MicroRNA-302d expressions in hepatoblastoma and clinical importance. J. Pediatr. Hematol. Oncol. 41, 7–12 (2019).

    Article  CAS  PubMed  Google Scholar 

  67. von Frowein, J. et al. MiR-492 regulates metastatic properties of hepatoblastoma via CD44. Liver Int. 38, 1280–1291 (2018).

    Article  Google Scholar 

  68. Cui, X. et al. Cross talk between RNA N6-methyladenosine methyltransferase-like 3 and miR-186 regulates hepatoblastoma progression through Wnt/β-catenin signalling pathway. Cell Prolif. 53, e12768 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Cairo, S. et al. Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer. Proc. Natl Acad. Sci. USA 107, 20471–20476 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Liu, B.-H. et al. Expression profiling identifies circular RNA signature in hepatoblastoma. Cell. Physiol. Biochem. 45, 706–719 (2018).

    Article  CAS  PubMed  Google Scholar 

  71. Kristensen, L. S., Jakobsen, T., Hager, H. & Kjems, J. The emerging roles of circRNAs in cancer and oncology. Nat. Rev. Clin. Oncol. 19, 188–206 (2022).

    Article  CAS  PubMed  Google Scholar 

  72. Nakagawara, A. et al. Molecular aspects of hepatoblastoma with special reference to alpha-fetoprotein and glypican-3. Expert Rev. Mol. Diagn. 19, 69–81 (2019).

    Google Scholar 

  73. Watanabe, M. et al. The role of AFP in hepatoblastoma: clinical significance and regulatory mechanisms. Int. J. Mol. Sci. 23, 2145 (2022).

    Google Scholar 

  74. Tanaka, M. et al. Liver stem/progenitor cells: their characteristics and regulatory mechanisms. J. Biochem. 149, 231–239 (2011).

    Article  CAS  PubMed  Google Scholar 

  75. Litten, J. B. & Tomlinson, G. E. Liver tumors in children. Oncologist 13, 812–820 (2008).

    Article  PubMed  Google Scholar 

  76. Lau, C. S. M., Mahendraraj, K. & Chamberlain, R. S. Hepatocellular carcinoma in the pediatric population: a population based clinical outcomes study involving 257 patients from the surveillance, epidemiology, and end result (SEER) database (1973–2011). HPB Surg. 2015, 670728 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Klein, S. D., DeMarchis, M., Linn, R. L., MacFarland, S. P. & Kalish, J. M. Occurrence of hepatoblastomas in patients with Beckwith–Wiedemann Spectrum (BWSp). Cancers 15, 2548 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kalish, J. M. et al. Surveillance recommendations for children with overgrowth syndromes and predisposition to wilms tumors and hepatoblastoma. Clin. Cancer Res. 23, e115–e122 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kalish, J. M. & Deardorff, M. A. Tumor screening in Beckwith-Wiedemann syndrome — to screen or not to screen? Am. J. Med. Genet. A 170, 2261–2264 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Brioude, F. et al. Clinical and molecular diagnosis, screening and management of Beckwith–Wiedemann syndrome: an international consensus statement. Nat. Rev. Endocrinol. 14, 229–249 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Brioude, F. et al. Overgrowth syndromes — clinical and molecular aspects and tumour risk. Nat. Rev. Endocrinol. 15, 299–311 (2019).

    Article  CAS  PubMed  Google Scholar 

  82. Yen, T. et al. in GeneReviews® (eds Adam, M. P. et al.) (University of Washington, 1998).

  83. Weiss, J. M. et al. NCCN Guidelines® insights: genetic/familial high-risk assessment: colorectal, version 1.2021. J. Natl Compr. Cancer Netw. 19, 1122–1132 (2021).

    Google Scholar 

  84. Duffy, K. A., Cohen, J. L., Elci, O. U. & Kalish, J. M. Development of the serum α-fetoprotein reference range in patients with Beckwith-Wiedemann spectrum. J. Pediatr. 212, 195–200.e2 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Hiyama, E. et al. Upfront or delayed surgery in resectable hepatoblastoma: analysis from the Children’s Hepatic Tumors International Collaboration database. eClinicalMedicine 76, 102811 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Trobaugh-Lotrario, A. D. et al. Outcomes of patients treated for hepatoblastoma with low alpha-fetoprotein and/or small cell undifferentiated histology: a report from the Children’s Hepatic Tumors International Collaboration (CHIC). Cancers 15, 467 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Schooler, G. R. et al. Imaging of pediatric liver tumors: a COG diagnostic imaging committee/SPR oncology committee white paper. Pediatr. Blood Cancer 70, e29965 (2023).

    Article  PubMed  Google Scholar 

  88. Knieling, F. et al. Spectrum, applicability and diagnostic capacity of contrast-enhanced ultrasound in pediatric patients and young adults after intravenous application — a retrospective trial. Ultraschall Med. 37, 619–626 (2016).

    Article  CAS  PubMed  Google Scholar 

  89. Jacob, J., Deganello, A., Sellars, M. E., Hadzic, N. & Sidhu, P. S. Contrast enhanced ultrasound (CEUS) characterization of grey-scale sonographic indeterminate focal liver lesions in pediatric practice. Ultraschall Med. 34, 529–540 (2013).

    Article  CAS  PubMed  Google Scholar 

  90. Fang, C. et al. Contrast-enhanced ultrasound of benign and malignant liver lesions in children. Pediatr. Radiol. 51, 2181–2197 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Schooler, G. R. et al. Pediatric hepatoblastoma, hepatocellular carcinoma, and other hepatic neoplasms: consensus imaging recommendations from American College of Radiology Pediatric Liver Reporting and Data System (LI-RADS) working group. Radiology 296, 493–497 (2020).

    Article  PubMed  Google Scholar 

  92. Towbin, A. J. et al. 2017 PRETEXT: radiologic staging system for primary hepatic malignancies of childhood revised for the Paediatric Hepatic International Tumour Trial (PHITT). Pediatr. Radiol. 48, 536–554 (2018). This revision of the PRETEXT staging system standardized radiological assessment of hepatoblastoma globally, ensuring consistent pre-treatment tumour evaluation across international collaborative groups.

    Article  PubMed  Google Scholar 

  93. Kolbe, A. B., Podberesky, D. J., Zhang, B. & Towbin, A. J. The impact of hepatocyte phase imaging from infancy to young adulthood in patients with a known or suspected liver lesion. Pediatr. Radiol. 45, 354–365 (2015).

    Article  PubMed  Google Scholar 

  94. Chavhan, G. B., Shelmerdine, S., Jhaveri, K. & Babyn, P. S. Liver MR imaging in children: current concepts and technique. RadioGraphics 36, 1517–1532 (2016).

    Article  PubMed  Google Scholar 

  95. Jhaveri, K. S. et al. Predictive value of chemical-shift MRI in distinguishing clear cell renal cell carcinoma from non–clear cell renal cell carcinoma and minimal-fat angiomyolipoma. Am. J. Roentgenol. 205, W79–W86 (2015).

    Article  Google Scholar 

  96. Sharma, K. et al. Role of diffusion weighted MRI (DW-MR) in detection of satellite lesions not detected with multiphase CT scans in hepatoblastoma and its implications for management. Indian J. Pediatr. 89, 968–974 (2022).

    Article  PubMed  Google Scholar 

  97. Padma, S., Sundaram, P. S. & Tewari, A. PET/CT in paediatric malignancies — an update. Indian J. Med. Paediatr. Oncol. 37, 131–140 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Chambers, G., Frood, R., Patel, C. & Scarsbrook, A. 18F-FDG PET-CT in paediatric oncology: established and emerging applications. Br. J. Radiol. 92, 20180584 (2019).

    Article  PubMed  Google Scholar 

  99. Cistaro, A. et al. A comparison between 18F-FDG PET/CT imaging and biological and radiological findings in restaging of hepatoblastoma patients. BioMed. Res. Int. 2013, 709037 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Yang, Y., Zhou, Z. & Li, Y. MRI-based deep learning model for differentiation of hepatic hemangioma and hepatoblastoma in early infancy. Eur. J. Pediatr. 182, 4365–4368 (2023).

    Article  PubMed  Google Scholar 

  101. Chen, Y. et al. Computed tomography imaging phenotypes of hepatoblastoma identified from radiomics signatures are associated with the efficacy of neoadjuvant chemotherapy. Pediatr. Radiol. 54, 58–67 (2024).

    Article  PubMed  Google Scholar 

  102. Roebuck, D. J. et al. 2005 PRETEXT: a revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group. Pediatr. Radiol. 37, 123–132 (2007).

    Article  PubMed  Google Scholar 

  103. Weldon, C. B. et al. Evaluation of the diagnostic biopsy approach for children with hepatoblastoma: a report from the Children’s Oncology Group AHEP 0731 Liver Tumor Committee. J. Pediatr. Surg. 55, 655–659 (2020).

    Article  PubMed  Google Scholar 

  104. Lungren, M. P. et al. Role of interventional radiology in managing pediatric liver tumors. Pediatr. Radiol. 48, 555–564 (2018).

    Article  PubMed  Google Scholar 

  105. Malogolowkin, M. H. et al. Complete surgical resection is curative for children with hepatoblastoma with pure fetal histology: a report from the Children’s Oncology Group. J. Clin. Oncol. 29, 3301–3306 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  106. Vasudevan, S. A. et al. Outcomes of children with well-differentiated fetal hepatoblastoma treated with surgery only: report from Children’s Oncology Group Trial, AHEP0731. J. Pediatr. Surg. 57, 251–256 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Manivel, C., Wick, M. R., Abenoza, P. & Dehner, L. P. Teratoid hepatoblastoma. the nosologic dilemma of solid embryonic neoplasms of childhood. Cancer 57, 2168–2174 (1986).

    Article  CAS  PubMed  Google Scholar 

  108. Zimmermann, A. Hepatoblastoma with cholangioblastic features (‘cholangioblastic hepatoblastoma’) and other liver tumors with bimodal differentiation in young patients. Med. Pediatr. Oncol. 39, 487–491 (2002).

    Article  PubMed  Google Scholar 

  109. Trobaugh-Lotrario, A. et al. Small cell undifferentiated histology does not adversely affect outcome in hepatoblastoma: a report from the Children’s Oncology Group (COG) AHEP0731 Study Committee. J. Clin. Oncol. 40, 459–467 (2022).

    Article  CAS  PubMed  Google Scholar 

  110. Haas, J. E., Feusner, J. H. & Finegold, M. J. Small cell undifferentiated histology in hepatoblastoma may be unfavorable. Cancer 92, 3130–3134 (2001).

    Article  CAS  PubMed  Google Scholar 

  111. Ranganathan, S., Lopez-Terrada, D. & Alaggio, R. Hepatoblastoma and pediatric hepatocellular carcinoma: an update. Pediatr. Dev. Pathol. 23, 79–95 (2020).

    Article  PubMed  Google Scholar 

  112. Lovvorn, H. N. et al. Defining hepatoblastoma responsiveness to induction therapy as measured by tumor volume and serum α-fetoprotein kinetics. J. Pediatr. Surg. 45, 121–128 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Umeda, K. et al. Prognostic and therapeutic factors influencing the clinical outcome of hepatoblastoma after liver transplantation: a single-institute experience. Pediatr. Transplant. https://doi.org/10.1111/petr.13113 (2018).

  114. Browne, M. et al. Survival after liver transplantation for hepatoblastoma: a 2-center experience. J. Pediatr. Surg. 43, 1973–1981 (2008).

    Article  PubMed  Google Scholar 

  115. Otte, J. B. et al. Liver transplantation for hepatoblastoma: results from the International Society of Pediatric Oncology (SIOP) study SIOPEL-1 and review of the world experience. Pediatr. Blood Cancer 42, 74–83 (2004).

    Article  CAS  PubMed  Google Scholar 

  116. Meyers, R. L., Katzenstein, H. M., Krailo, M., McGahren, E. D. & Malogolowkin, M. H. Surgical resection of pulmonary metastatic lesions in children with hepatoblastoma. J. Pediatr. Surg. 42, 2050–2056 (2007).

    Article  PubMed  Google Scholar 

  117. Katzenstein, H. M. et al. Doxorubicin in combination with cisplatin, 5-flourouracil, and vincristine is feasible and effective in unresectable hepatoblastoma: a Children’s Oncology Group study. Cancer 128, 1057–1065 (2022).

    Article  CAS  PubMed  Google Scholar 

  118. Katzenstein, H. M. et al. Upfront window vincristine/irinotecan treatment of high-risk hepatoblastoma: a report from the Children’s Oncology Group AHEP0731 study committee. Cancer 123, 2360–2367 (2017).

    Article  CAS  PubMed  Google Scholar 

  119. Brown, J. et al. Pretreatment prognostic factors for children with hepatoblastoma — results from the International Society of Paediatric Oncology (SIOP) study SIOPEL 1. Eur. J. Cancer 36, 1418–1425 (2000).

    Article  CAS  PubMed  Google Scholar 

  120. Schnater, J. M. et al. Surgical view of the treatment of patients with hepatoblastoma. Cancer 94, 1111–1120 (2002).

    Article  PubMed  Google Scholar 

  121. Perilongo, G. et al. Risk-adapted treatment for childhood hepatoblastoma: final report of the second study of the International Society of Paediatric Oncology — SIOPEL 2. Eur. J. Cancer 40, 411–421 (2004).

    Article  CAS  PubMed  Google Scholar 

  122. Zsíros, J. et al. Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR Study. J. Clin. Oncol. 28, 2584–2590 (2010).

    Article  PubMed  Google Scholar 

  123. Brock, P. R. et al. Sodium thiosulfate for protection from cisplatin-induced hearing loss. N. Engl. J. Med. 378, 2376–2385 (2018). This practice-changing trial demonstrated that sodium thiosulfate significantly reduces cisplatin-induced hearing loss in children with hepatoblastoma without compromising survival outcomes, addressing a major quality-of-life concern.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Zsiros, J. et al. Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol. 14, 834–842 (2013). This influential SIOPEL-4 trial demonstrated that intensified, dose-dense chemotherapy dramatically improved outcomes for children with high-risk hepatoblastoma, establishing a new standard of care for this challenging patient population.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Sasaki, F. et al. Outcome of hepatoblastoma treated with the JPLT-1 (Japanese Study Group for Pediatric Liver Tumor) protocol-1: a report from the Japanese Study Group for Pediatric Liver Tumor. J. Pediatr. Surg. 37, 851–856 (2002).

    Article  CAS  PubMed  Google Scholar 

  126. Hiyama, E. et al. Outcome and late complications of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor 2 protocol. J. Clin. Oncol. 38, 2488–2498 (2020).

    Article  PubMed  Google Scholar 

  127. Saeki, I. et al. Successful treatment of young childhood standard-risk hepatoblastoma with cisplatin monotherapy using a central review system. Pediatr. Blood Cancer 11, e31255 (2024).

    Article  Google Scholar 

  128. Hishiki, T. et al. Feasibility of real-time central surgical review for patients with advanced-stage hepatoblastoma in the JPLT3 Trial. Children 9, 234 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Miyazaki, O. et al. Usefulness of central radiologic review in clinical trials of children with hepatoblastoma. Pediatr. Radiol. 53, 367–377 (2023).

    Article  PubMed  Google Scholar 

  130. Watanabe, K. et al. Feasibility of dose-dense cisplatin-based chemotherapy in Japanese children with high-risk hepatoblastoma: analysis of the JPLT3-H pilot study. Pediatr. Blood Cancer 69, e29389 (2022).

    Article  CAS  PubMed  Google Scholar 

  131. Angiolillo, A. L. et al. A phase I clinical, pharmacologic, and biologic study of thrombopoietin and granulocyte colony-stimulating factor in children receiving ifosfamide, carboplatin, and etoposide chemotherapy for recurrent or refractory solid tumors: a Children’s Oncology Group experience. Clin. Cancer Res. 11, 2644–2650 (2005).

    Article  CAS  PubMed  Google Scholar 

  132. Zsíros, J. et al. Efficacy of irinotecan single drug treatment in children with refractory or recurrent hepatoblastoma — a phase II trial of the Childhood Liver Tumour Strategy Group (SIOPEL). Eur. J. Cancer 48, 3456–3464 (2012).

    Article  PubMed  Google Scholar 

  133. Semeraro, M. et al. Relapses in hepatoblastoma patients: clinical characteristics and outcome-experience of the International Childhood Liver Tumour Strategy Group (SIOPEL). Eur. J. Cancer 49, 915–922 (2013).

    Article  CAS  PubMed  Google Scholar 

  134. O’Neill, A. F. et al. The RELIVE consortium for relapsed or refractory pediatric hepatoblastoma and hepatocellular carcinoma: a scoping review of the problem and a proposed solution problem and a proposed solution. eClinicalMedicine 69, 102446 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  135. Fung, K. F. K. et al. Management of acute intra-abdominal hemorrhage in ruptured hepatoblastoma with transarterial embolization using calibrated gelfoam particles. Pediatr. Blood Cancer 70, e30019 (2023).

    Article  CAS  PubMed  Google Scholar 

  136. Oue, T. et al. Transcatheter arterial chemoembolization in the treatment of hepatoblastoma. J. Pediatr. Surg. 33, 1771–1775 (1998).

    Article  CAS  PubMed  Google Scholar 

  137. Wang, S. et al. First experience of high-intensity focused ultrasound combined with transcatheter arterial embolization as local control for hepatoblastoma. Hepatology 59, 170–177 (2014).

    Article  PubMed  Google Scholar 

  138. Yevich, S. et al. Reiterative radiofrequency ablation in the management of pediatric patients with hepatoblastoma metastases to the lung, liver, or bone. Cardiovasc. Interv. Radiol. 42, 41–47 (2019).

    Article  Google Scholar 

  139. Kannappan, O. et al. Portal vein embolization for future liver remnant enhancement and combined modality treatment for the management of post-hepatic resection biliary fistula in an 18-month old child with hepatoblastoma. Front. Surg. 6, 54 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Le, N. et al. Right trisegmentectomy after portal vein embolization in a high-risk toddler with hepatoblastoma. Pediatr. Surg. Int. 34, 573–578 (2018).

    Article  PubMed  Google Scholar 

  141. Zhang, Y.-T. et al. Novel treatment of refractory / recurrent pulmonary hepatoblastoma. Pediatr. Int. 62, 324–329 (2020).

    Article  CAS  PubMed  Google Scholar 

  142. Katzenstein, H. M. et al. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children’s Oncology Group, multicentre, phase 3 trial. Lancet Oncol. 20, 719–727 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Kastenberg, Z. J. et al. Critical elements of pediatric liver cancer surgery. Semin. Pediatr. Surg. 32, 151340 (2023).

    Article  PubMed  Google Scholar 

  144. Qureshi, S. S. et al. Feasibility of nonanatomical liver resection in diligently selected patients with hepatoblastoma and comparison of outcomes with anatomic resection. Eur. J. Pediatr. Surg. 31, 236–244 (2021).

    Article  PubMed  Google Scholar 

  145. Aronson, D. C. et al. Microscopically positive resection margin after hepatoblastoma resection: what is the impact on prognosis? A Childhood Liver Tumours Strategy Group (SIOPEL) report. Eur. J. Cancer 106, 126–132 (2019).

    Article  PubMed  Google Scholar 

  146. Ren, X., Li, H., Diao, M., Xu, H. & Li, L. Impact of microscopically margin-positive resection on survival in children with hepatoblastoma after hepatectomy: a retrospective cohort study. Int. J. Clin. Oncol. 25, 765–773 (2020).

    Article  PubMed  Google Scholar 

  147. Feng, J. et al. Assessment of survival of pediatric patients with hepatoblastoma who received chemotherapy following liver transplant or liver resection. JAMA Netw. Open 2, e1912676 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Cruz, R. J., Sasatomi, E., Hughes, C. B., Humar, A. & Minervini, M. Allograft involvement with posttransplant lymphoproliferative disorders (PTLD) in recipients of liver transplant: a clinicopathological analysis of 17 cases. Liver Transpl. 30, 862–865 (2024).

    Article  PubMed  Google Scholar 

  149. Pham, T. A., Gallo, A. M., Concepcion, W., Esquivel, C. O. & Bonham, C. A. Effect of liver transplant on long-term disease-free survival in children with hepatoblastoma and hepatocellular cancer. JAMA Surg. 150, 1150–1158 (2015).

    Article  PubMed  Google Scholar 

  150. Stefanowicz, M. et al. Risk for recurrence in long-term follow-up of children after liver transplantation for hepatoblastoma or hepatocellular carcinoma. Children 11, 193 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Murphy, A. J. et al. Imaging analysis of hepatoblastoma resectability across neoadjuvant chemotherapy. J. Pediatr. Surg. 48, 1239–1248 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Fleming, A. M. et al. Aggressive pursuit of no evidence of disease status in hepatoblastoma improves survival: an observational study. J. Pediatr. Surg. 58, 1081–1087 (2023).

    Article  PubMed  Google Scholar 

  153. Abdelhafeez, A. H. et al. Feasibility of indocyanine green-guided localization of pulmonary nodules in children with solid tumors. Pediatr. Blood Cancer 70, e30437 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Farooqui, Z. et al. Quality of life outcomes for patients who underwent conventional resection and liver transplantation for locally advanced hepatoblastoma. Children 10, 890 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  155. Cussa, D. et al. Long-term outcomes and health-related quality of life 20 years after pediatric liver transplantation. Updates Surg. 75, 1549–1557 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Dieffenbach, B. V. et al. Cumulative burden of late, major surgical intervention in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study (CCSS) cohort. Lancet Oncol. 24, 691–700 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  157. Illiano, M. et al. Long-term morbidity and mortality in 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies. Hepatol. Int. 16, 125–134 (2022).

    Article  CAS  PubMed  Google Scholar 

  158. Beyea, J. A. et al. Long-term incidence and predictors of significant hearing loss requiring hearing assistive devices among childhood cancer survivors: a population-based study. J. Clin. Oncol. 38, 2639–2646 (2020).

    Article  PubMed  Google Scholar 

  159. Rojas, Y. et al. Relapse surveillance in AFP-positive hepatoblastoma: re-evaluating the role of imaging. Pediatr. Radiol. 44, 1275–1280 (2014).

    Article  PubMed  Google Scholar 

  160. Wu, P. V. & Rangaswami, A. Current approaches in hepatoblastoma — new biological insights to inform therapy. Curr. Oncol. Rep. 24, 1209–1218 (2022).

    Article  CAS  PubMed  Google Scholar 

  161. Li, W. et al. Redirecting T cells to glypican-3 with 4-1BB zeta chimeric antigen receptors results in Th1 polarization and potent antitumor activity. Hum. Gene Ther. 28, 437–448 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Guo, J. & Tang, Q. Recent updates on chimeric antigen receptor T cell therapy for hepatocellular carcinoma. Cancer Gene Ther. 28, 1075–1087 (2021).

    Article  CAS  PubMed  Google Scholar 

  163. Yoshida, M. et al. Clinicopathological study of surgery for pulmonary metastases of hepatoblastoma with indocyanine green fluorescent imaging. Pediatr. Blood Cancer 69, e29488 (2022).

    Article  CAS  PubMed  Google Scholar 

  164. Pio, L. et al. Identification of pediatric tumors intraoperatively using indocyanine green (ICG). Ann. Surg. Oncol. 30, 7789–7798 (2023). This innovative study demonstrated the clinical utility of ICG fluorescence guidance for improving surgical precision in pediatric tumour resection and metastasectomy, representing a significant advancement in surgical technique.

    Article  PubMed  Google Scholar 

  165. Hiyama, E. Fluorescence image-guided navigation surgery using indocyanine green for hepatoblastoma. Children 8, 1015 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  166. Kalish, J. M. et al. Update on surveillance for Wilms tumor and hepatoblastoma in Beckwith-Wiedemann syndrome and other predisposition syndromes. Clin. Cancer Res. 30, 5260–5269 (2024).

    Article  CAS  PubMed  Google Scholar 

  167. Lautz, T. B. et al. Successful nontransplant resection of POST-TEXT III and IV hepatoblastoma. Cancer 117, 1976–1983 (2011).

    Article  PubMed  Google Scholar 

  168. Fonseca, A. et al. Extreme hepatic resections for the treatment of advanced hepatoblastoma: are planned close margins an acceptable approach? Pediatr. Blood Cancer. https://doi.org/10.1002/pbc.26820 (2018).

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Luca Pio & Andrew J. Murphy

  2. Paediatric Surgery Unit, Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France

    Luca Pio & Sophie Branchereau

  3. Department of Paediatric Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA

    Allison F. O’Neill

  4. Department of Paediatric Radiology, Leeds Children’s Hospital, Leeds, UK

    Helen Woodley

  5. Division of General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Gregory Tiao

  6. Department of Paediatric Radiology, Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France

    Stefanie Franchi-Abella

  7. Department of Children and Adolescents Oncology, Gustave Roussy, University Paris Saclay and Radiation Epidemiology Team, CESO, Inserm U1018, Villejuif, France

    Brice Fresneau

  8. Department of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan

    Kenichiro Watanabe

  9. Pathology Department, Ospedale Paediatrico Bambino Gesù IRCCS, Rome, Italy

    Rita Alaggio

  10. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

    Dolores Lopez-Terrada

  11. Department of Biomedical Science, Natural Science Center for Basic Research and Development (N-BARD), Hiroshima University, Hiroshima, Japan

    Eiso Hiyama

Authors
  1. Luca Pio
    View author publications

    Search author on:PubMed Google Scholar

  2. Allison F. O’Neill
    View author publications

    Search author on:PubMed Google Scholar

  3. Helen Woodley
    View author publications

    Search author on:PubMed Google Scholar

  4. Andrew J. Murphy
    View author publications

    Search author on:PubMed Google Scholar

  5. Gregory Tiao
    View author publications

    Search author on:PubMed Google Scholar

  6. Stefanie Franchi-Abella
    View author publications

    Search author on:PubMed Google Scholar

  7. Brice Fresneau
    View author publications

    Search author on:PubMed Google Scholar

  8. Kenichiro Watanabe
    View author publications

    Search author on:PubMed Google Scholar

  9. Rita Alaggio
    View author publications

    Search author on:PubMed Google Scholar

  10. Dolores Lopez-Terrada
    View author publications

    Search author on:PubMed Google Scholar

  11. Eiso Hiyama
    View author publications

    Search author on:PubMed Google Scholar

  12. Sophie Branchereau
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Introduction (L.P.); Epidemiology (A.F.O. and H.W.); Diagnosis, screening and prevention (A.F.O., H.W. and S.F.-A.); Mechanisms (R.A., E.H. and D.L.-T.); Management (A.F.O., A.J.M., B.F., G.T. and K.W.); Quality of life (L.P.); Outlook (S.B.). All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Luca Pio.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Disease Primers thanks P. Czauderna, M. Dandapani and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pio, L., O’Neill, A.F., Woodley, H. et al. Hepatoblastoma. Nat Rev Dis Primers 11, 36 (2025). https://doi.org/10.1038/s41572-025-00620-7

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41572-025-00620-7

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer