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Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency
- Source :
- Hepatology (Baltimore, Md.). 44(2)
- Publication Year :
- 2006
-
Abstract
- 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 nonrelated 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. (HEPATOLOGY 2006;44:478–486.)
- Subjects :
- Male
medicine.medical_specialty
Carcinoma, Hepatocellular
Biopsy
Benign Recurrent Intrahepatic Cholestasis
Gastroenterology
Internal medicine
Medicine
Humans
ABCB11
ATP Binding Cassette Transporter, Subfamily B, Member 11
Hepatology
medicine.diagnostic_test
business.industry
Liver Neoplasms
Progressive familial intrahepatic cholestasis
Infant, Newborn
Infant
DNA, Neoplasm
medicine.disease
Prognosis
Bile Salt Export Pump
Immunohistochemistry
Neonatal hepatitis
Gene Expression Regulation, Neoplastic
Hepatocellular carcinoma
Child, Preschool
Mutation
Disease Progression
ATP-Binding Cassette Transporters
Female
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 02709139
- Volume :
- 44
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Hepatology (Baltimore, Md.)
- Accession number :
- edsair.doi.dedup.....a2acc0a0771aec0de838059ce5438b21