Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency

A. S. Knisely*, Sandra S. Strautnieks, Yvonne Meier, Bruno Stieger, Jane A. Byrne, Bernard C. Portmann, Laura N. Bull, Ludmila Pawlikowska, Banu Bilezikçi, Figen Özçay, Aranka László, László Tiszlavicz, Lynette Moore, Jeremy Raftos, Henrik Arnell, Björn Fischler, Antal Németh, Nikos Papadogiannakis, Joanna Cielecka-Kuszyk, Irena JankowskaJoanna Pawłowska, Hector Melín-Aldana, Karan M. Emerick, Peter F. Whitington, Giorgina Mieli-Vergani, Richard J. Thompson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

307 Scopus citations


Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational-analysis studies could demonstrate that deficiency of the canalicular bile acid transporter bile salt export pump (BSEP) and mutation in ABCB11, encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC)-or "neonatal hepatitis" suggesting PFIC-that was associated with HCC in young children. We studied 11 cases of pediatric HCC in the setting of PFIC or "neonatal hepatitis" suggesting PFIC. Archival liver were retrieved and immunostained for BSEP. Mutational analysis of ABCB11 was performed in leukocyte DNA from available patients and parents. Among the 11 non-related children studied aged 13-52 months at diagnosis of HCC, 9 (and a full sibling, with neonatal hepatitis suggesting PFIC, of a tenth from whom liver was not available) had immunohistochemical evidence of BSEP deficiency; the eleventh child did not. Mutations in ABCB11 were demonstrated in all patients with BSEP deficiency in whom leukocyte DNA could be studied (n = 7). These mutations were confirmed in the parents (n = 14). With respect to the other 3 children with BSEP deficiency, mutations in ABCB11 were demonstrated in all 5 parents in whom leukocyte DNA could be studied. Thirteen different mutations were found. In conclusion, PFIC associated with BSEP deficiency represents a previously unrecognized risk for HCC in young children. Immunohistochemical evidence of BSEP deficiency correlates well with demonstrable mutation in ABCB11.

Original languageEnglish (US)
Pages (from-to)478-486
Number of pages9
Issue number2
StatePublished - Aug 2006

ASJC Scopus subject areas

  • Hepatology


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