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Hepatocellular Carcinoma in Paediatric Patients with Alagille Syndrome: Case Series and Review of Literature

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Fig. 1



Alfa-feto protein


Alagille syndrome


Chronic liver disease


Hepatocellular carcinoma


Liver transplantation


Transcatheter arterial chemoembolization


  1. 1.

    Kamath BM, Schwarz KB, Hadzić N. Alagille syndrome and liver transplantation. Pediatr Gastroenterol Nutr. 2010;50(1):11–5.

    Google Scholar 

  2. 2.

    Turnpenny PD, Ellard S. Alagille syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2012;20(3):251–7.

    CAS  PubMed  Google Scholar 

  3. 3.

    Kamath BM, Spinner NB, Piccoli AD. Alagille syndrome. In: Suchy FJ, Sokol RJ, Balistreri WF, editors. Liver disease in children. 4th ed. Cambridge: Cambridge Univ. Press; 2014. p. 216–34.

    Google Scholar 

  4. 4.

    Pacheco MC, Monroe EJ, Horslen SP. Hepatic adenoma arising in a patient with Alagille syndrome: a case report. Pediatr Dev Pathol. 2018;21(6):585–9.

    PubMed  Google Scholar 

  5. 5.

    Schwarzenberg SJ, Grothe RM, Sharp HL, Snover DC, Freese D. Long-term complications of arteriohepatic dysplasia. Am J Med. 1992;93(2):171–6.

    CAS  PubMed  Google Scholar 

  6. 6.

    Rabinovitz M, Imperial JC, Schade RR, Van Thiel DH. Hepatocellular carcinoma in Alagille’s syndrome: a family study. J Pediatr Gastroenterol Nutr. 1989;8(1):26–30.

    CAS  PubMed  Google Scholar 

  7. 7.

    Kim B, Park SH, Ran Yang H, Kee Seo J, Sun Kim W, Chi JG. Hepatocellular carcinoma occurring in Alagille syndrome. Pathol Res Pract. 2005;201(1):55–60.

    PubMed  Google Scholar 

  8. 8.

    Khanna R, Verma SK. Pediatric hepatocellular carcinoma. World J Gastroenterol. 2018;24(35):3980–99.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Theise ND, Curado MP, Franceschi S, et al. Hepatocellular carcinoma. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC Press; 2010.

    Google Scholar 

  10. 10.

    Valamparampil JJ, Reddy MS, Shanmugam N, Vij M, Kanagavelu RG, Rela M. Living donor liver transplantation in Alagille syndrome—single center experience from South Asia. Pediatr Transplant. 2019;23:e13579.

    PubMed  Google Scholar 

  11. 11.

    Ong E, Williams SM, Anderson JC, Kaplan PA. MR imaging of a hepatoma associated with Alagille syndrome. J Comput Assist Tomogr. 1986;10(6):1047–9.

    CAS  PubMed  Google Scholar 

  12. 12.

    Kaufman SS. Hepatocarcinoma in a child with the Alagille syndrome. Arch Pediatr Adolesc Med. 1987;141(6):698.

    CAS  Google Scholar 

  13. 13.

    Békássy AN, Garwicz S, Wiebe T, Hägerstrand I, Jensen OA. Hepatocellular carcinoma associated with arteriohepatic dysplasia in a 4-year-old girl. Med Pediatr Oncol. 1992;20(1):78–83.

    PubMed  Google Scholar 

  14. 14.

    Keeffe EB, Pinson CW, Ragsdale J, Zonana J. Hepatocellular carcinoma in arteriohepatic dysplasia. Am J Gastroenterol. 1993;88(9):1446–9.

    CAS  PubMed  Google Scholar 

  15. 15.

    Bhadri VA, Stormon MO, Arbuckle S, Lam AH, Gaskin KJ, Shun A. Hepatocellular carcinoma in children with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2005;41(5):676–8.

    PubMed  Google Scholar 

  16. 16.

    Wetli SC, Gralla ES, Schibli S, Stranzinger E. Hepatocellular carcinoma and regenerating nodule in a 3-year-old child with Alagille syndrome. Pediatr Radiol. 2010;40(10):1696–8.

    PubMed  Google Scholar 

  17. 17.

    Pham TA, Gallo AM, Concepcion W, Esquivel CO, Bonham CA. Effect of liver transplant on long-term disease-free survival in children with hepatoblastoma and hepatocellular cancer. JAMA Surg. 2015;150(12):1150–8.

    PubMed  Google Scholar 

  18. 18.

    Geramizadeh B, Kashkooe A, Bahador A, et al. Pediatric hepatocellular carcinoma, a single center study from the South of Iran: case series. Hepat Mon. 2017;17(8).

  19. 19.

    Vinayak R, Cruz RJ, Ranganathan S, et al. Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multicenter and single-center experience (1981–2015). Liver Transpl. 2017;23(12):1577–88.

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Weiss KE, Sze DY, Rangaswami AA, et al. Transarterial chemoembolization in children to treat unresectable hepatocellular carcinoma. Pediatr Transplant. 2018;22(4):e13187.

    PubMed  Google Scholar 

  21. 21.

    D’Souza AM, Shah R, Gupta A, et al. Surgical management of children and adolescents with upfront completely resected hepatocellular carcinoma. Pediatr Blood Cancer. 2018;65(11):e27293.

    PubMed  Google Scholar 

  22. 22.

    Beaunoyer M, Vanatta JM, Ogihara M, et al. Outcomes of transplantation in children with primary hepatic malignancy: outcomes of OLT in children with liver cancer. Pediatr Transplant. 2007;11(6):655–60.

    PubMed  Google Scholar 

  23. 23.

    Kamath BM, Yin W, Miller H, Anand R, Rand EB, Alonso E, et al. Outcomes of liver transplantation for patients with alagille syndrome: the studies of pediatric liver transplantation experience. Liver Transpl. 2012;18(8):940–8.

    PubMed  Google Scholar 

  24. 24.

    Kamath BM, Baker A, Houwen R, Todorova L, Kerkar N. Systematic review: the epidemiology, natural history, and burden of Alagille syndrome. JPGN. 2018;67(2):148–56.

    PubMed  Google Scholar 

  25. 25.

    Schmid I, von Schweinitz D. Pediatric hepatocellular carcinoma: challenges and solutions. J Hepatocell Carcinoma. 2017;4:15–21.

    PubMed  PubMed Central  Google Scholar 

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Correspondence to Joseph J. Valamparampil.

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Fig. 2A Well differentiated hepatocellular carcinoma with pale eosinophilic cytoplasm and sclerosis. 2B Glypican 3 immunopositivity in the tumor. 2C CK7 immunostaining highlighting the loss of interlobular bile ducts in explant liver. 2D Masson trichrome demonstrating cirrhosis in the explant liver (PNG 1551 kb)


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Valamparampil, J.J., Shanmugam, N., Vij, M. et al. Hepatocellular Carcinoma in Paediatric Patients with Alagille Syndrome: Case Series and Review of Literature. J Gastrointest Canc 51, 1047–1052 (2020).

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