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Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism

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Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism. / Grammatikopoulos, Tassos; Deheragoda, Maesha; Strautnieks, Sandra; Neves Souza, Lara; Hinds, Rupert; Thompson, Richard J.; Hadzic, Nedim.

In: Journal of Pediatrics, 20.06.2018.

Research output: Contribution to journalArticle

Harvard

Grammatikopoulos, T, Deheragoda, M, Strautnieks, S, Neves Souza, L, Hinds, R, Thompson, RJ & Hadzic, N 2018, 'Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism', Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2018.05.009

APA

Grammatikopoulos, T., Deheragoda, M., Strautnieks, S., Neves Souza, L., Hinds, R., Thompson, R. J., & Hadzic, N. (2018). Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism. Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2018.05.009

Vancouver

Grammatikopoulos T, Deheragoda M, Strautnieks S, Neves Souza L, Hinds R, Thompson RJ et al. Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism. Journal of Pediatrics. 2018 Jun 20. https://doi.org/10.1016/j.jpeds.2018.05.009

Author

Grammatikopoulos, Tassos ; Deheragoda, Maesha ; Strautnieks, Sandra ; Neves Souza, Lara ; Hinds, Rupert ; Thompson, Richard J. ; Hadzic, Nedim. / Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism. In: Journal of Pediatrics. 2018.

Bibtex Download

@article{9a6d5001d573418fa55d3c218741a6d3,
title = "Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism",
abstract = "Objective To assess whether prolonged neonatal cholestasis, described in congenital hypopituitarism and septo-optic dysplasia (SOD), is associated with altered expression of selected canalicular ectoenzymes and canalicular transport proteins. Study design Children with congenital hypopituitarism (n = 21), SOD (n = 18), and cholestasis seen in our center over 26 years were reviewed. Histopathologic findings in archival liver biopsy specimens were assessed (n = 10) and in those with low/normal levels of serum γ-glutamyltransferase (GGT) activity despite conjugated hyperbilirubinemia, expression of canalicular ectoenzymes and canalicular transport proteins was evaluated immunohistochemically. Results Patients presented at a median age of 8 weeks (range 3-20 weeks) with median total bilirubin 116 µmol/L (45-287 µmol/L), GGT 95 IU/L (25-707 UI/L), and serum cortisol 51 nmol/L (17-240 nmol/L). All but 3 had low free thyroxin (median 9.6 pmol/L [6.8-26.9]) with increased thyroid-stimulating hormone levels (median 5.95 mU/L [<0.1-9.24]). Liver histologic features included moderate-to-severe intralobular cholestasis with nonspecific hepatitis, giant-cell transformation of hepatocytes, and fibrosis. In all, immunohistochemical staining for canalicular ectoenzymes and canalicular transport proteins revealed a degree of reduced expression, associated with normal serum GGT values in 6 of the 10 patients, and another 6 nonbiopsied infants with cholestasis also had low/normal serum GGT activity. Sequencing of ABCB11 and ATP8B1 performed in 6 of the biopsied patients did not identify pathogenic mutations. Following replacement therapy, biochemical evidence of hepatobiliary injury resolved in all children within a median period of 6 months. Conclusion Hepatobiliary involvement in congenital hypopituitarism associated with SOD has a good prognosis, but its etiology remains uncertain. Immunohistochemical expression of canalicular transport proteins was reduced in available liver samples.",
keywords = "cholestasis, congenital hypopituitarism, septo-optic dysplasia, canalicular ectoenzymes, canalicular transport proteins",
author = "Tassos Grammatikopoulos and Maesha Deheragoda and Sandra Strautnieks and {Neves Souza}, Lara and Rupert Hinds and Thompson, {Richard J.} and Nedim Hadzic",
year = "2018",
month = jun,
day = "20",
doi = "10.1016/j.jpeds.2018.05.009",
language = "English",
journal = "Journal of Pediatrics",
issn = "0022-3476",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism

AU - Grammatikopoulos, Tassos

AU - Deheragoda, Maesha

AU - Strautnieks, Sandra

AU - Neves Souza, Lara

AU - Hinds, Rupert

AU - Thompson, Richard J.

AU - Hadzic, Nedim

PY - 2018/6/20

Y1 - 2018/6/20

N2 - Objective To assess whether prolonged neonatal cholestasis, described in congenital hypopituitarism and septo-optic dysplasia (SOD), is associated with altered expression of selected canalicular ectoenzymes and canalicular transport proteins. Study design Children with congenital hypopituitarism (n = 21), SOD (n = 18), and cholestasis seen in our center over 26 years were reviewed. Histopathologic findings in archival liver biopsy specimens were assessed (n = 10) and in those with low/normal levels of serum γ-glutamyltransferase (GGT) activity despite conjugated hyperbilirubinemia, expression of canalicular ectoenzymes and canalicular transport proteins was evaluated immunohistochemically. Results Patients presented at a median age of 8 weeks (range 3-20 weeks) with median total bilirubin 116 µmol/L (45-287 µmol/L), GGT 95 IU/L (25-707 UI/L), and serum cortisol 51 nmol/L (17-240 nmol/L). All but 3 had low free thyroxin (median 9.6 pmol/L [6.8-26.9]) with increased thyroid-stimulating hormone levels (median 5.95 mU/L [<0.1-9.24]). Liver histologic features included moderate-to-severe intralobular cholestasis with nonspecific hepatitis, giant-cell transformation of hepatocytes, and fibrosis. In all, immunohistochemical staining for canalicular ectoenzymes and canalicular transport proteins revealed a degree of reduced expression, associated with normal serum GGT values in 6 of the 10 patients, and another 6 nonbiopsied infants with cholestasis also had low/normal serum GGT activity. Sequencing of ABCB11 and ATP8B1 performed in 6 of the biopsied patients did not identify pathogenic mutations. Following replacement therapy, biochemical evidence of hepatobiliary injury resolved in all children within a median period of 6 months. Conclusion Hepatobiliary involvement in congenital hypopituitarism associated with SOD has a good prognosis, but its etiology remains uncertain. Immunohistochemical expression of canalicular transport proteins was reduced in available liver samples.

AB - Objective To assess whether prolonged neonatal cholestasis, described in congenital hypopituitarism and septo-optic dysplasia (SOD), is associated with altered expression of selected canalicular ectoenzymes and canalicular transport proteins. Study design Children with congenital hypopituitarism (n = 21), SOD (n = 18), and cholestasis seen in our center over 26 years were reviewed. Histopathologic findings in archival liver biopsy specimens were assessed (n = 10) and in those with low/normal levels of serum γ-glutamyltransferase (GGT) activity despite conjugated hyperbilirubinemia, expression of canalicular ectoenzymes and canalicular transport proteins was evaluated immunohistochemically. Results Patients presented at a median age of 8 weeks (range 3-20 weeks) with median total bilirubin 116 µmol/L (45-287 µmol/L), GGT 95 IU/L (25-707 UI/L), and serum cortisol 51 nmol/L (17-240 nmol/L). All but 3 had low free thyroxin (median 9.6 pmol/L [6.8-26.9]) with increased thyroid-stimulating hormone levels (median 5.95 mU/L [<0.1-9.24]). Liver histologic features included moderate-to-severe intralobular cholestasis with nonspecific hepatitis, giant-cell transformation of hepatocytes, and fibrosis. In all, immunohistochemical staining for canalicular ectoenzymes and canalicular transport proteins revealed a degree of reduced expression, associated with normal serum GGT values in 6 of the 10 patients, and another 6 nonbiopsied infants with cholestasis also had low/normal serum GGT activity. Sequencing of ABCB11 and ATP8B1 performed in 6 of the biopsied patients did not identify pathogenic mutations. Following replacement therapy, biochemical evidence of hepatobiliary injury resolved in all children within a median period of 6 months. Conclusion Hepatobiliary involvement in congenital hypopituitarism associated with SOD has a good prognosis, but its etiology remains uncertain. Immunohistochemical expression of canalicular transport proteins was reduced in available liver samples.

KW - cholestasis

KW - congenital hypopituitarism

KW - septo-optic dysplasia

KW - canalicular ectoenzymes

KW - canalicular transport proteins

U2 - 10.1016/j.jpeds.2018.05.009

DO - 10.1016/j.jpeds.2018.05.009

M3 - Article

JO - Journal of Pediatrics

JF - Journal of Pediatrics

SN - 0022-3476

ER -

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