Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder

Simon P. Horslen, Timothy C. McCowan, Timothy C. Goertzen, Phyllis Irene Warkentin, Hung Bo Cai, Stephen C. Strom, Ira J. Fox

Research output: Contribution to journalArticle

243 Citations (Scopus)

Abstract

Objective. Transplantation of isolated hepatocytes in animal models has been shown to correct inborn errors of metabolism. Based on these studies and our experience with hepatocyte transplantation in a child with Crigler-Najjar syndrome, isolated hepatocyte transplantation was performed to attempt metabolic reconstitution in a male infant with severe ornithine transcarbamylase (OTC) deficiency. Methods. An infant with an antenatal diagnosis of OTC deficiency was managed intensively to prevent hyperammonemia. Isolated hepatocytes were obtained by collagenase perfusion of donated livers not used for transplantation. Hepatocytes were infused in batches over the first 4 weeks of life via an umbilical venous catheter positioned in the portal vein. Immunosuppression consisted of tacrolimus and corticosteroids. Results. Over 4 billion viable hepatocytes were transplanted during the first 3.5 weeks of life. A period of metabolic stability was achieved between days 20 and 31 during which normal protein intake was tolerated while phenylbutyrate was weaned. During this time, plasma ammonia and glutamine remained within normal limits. Hyperammonemia reappeared abruptly on day 31 of life. Protein tolerance diminished to baseline; metabolic stability was subsequently reattained only following successful liver transplantation at 6 months of age. Conclusions. Isolated hepatocyte transplantation appeared to result in temporary relief of hyperammonemia and protein intolerance attributable to OTC deficiency. The metabolic stability achieved was lost after 11 days presumably because of rejection of the transplanted cells because of insufficient immunosuppression. Future attempts at isolated hepatocyte transplantation for inborn errors of metabolism in humans should include adequate immunosuppression and a liver biopsy as a means of proving hepatocyte engraftment and function.

Original languageEnglish (US)
Pages (from-to)1262-1267
Number of pages6
JournalPediatrics
Volume111
Issue number6 I
DOIs
StatePublished - Jun 1 2003

Fingerprint

Inborn Urea Cycle Disorder
Hepatocytes
Transplantation
Ornithine Carbamoyltransferase Deficiency Disease
Hyperammonemia
Immunosuppression
Inborn Errors Metabolism
Crigler-Najjar Syndrome
Phenylbutyrates
Umbilicus
Proteins
Liver
Tacrolimus
Collagenases
Portal Vein
Glutamine
Prenatal Diagnosis
Ammonia
Liver Transplantation
Adrenal Cortex Hormones

Keywords

  • Hepatocyte transplantation
  • Infant
  • Ornthine transcarbamylase deficiency
  • Urea cycle disorder

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Horslen, S. P., McCowan, T. C., Goertzen, T. C., Warkentin, P. I., Cai, H. B., Strom, S. C., & Fox, I. J. (2003). Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. Pediatrics, 111(6 I), 1262-1267. https://doi.org/10.1542/peds.111.6.1262

Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. / Horslen, Simon P.; McCowan, Timothy C.; Goertzen, Timothy C.; Warkentin, Phyllis Irene; Cai, Hung Bo; Strom, Stephen C.; Fox, Ira J.

In: Pediatrics, Vol. 111, No. 6 I, 01.06.2003, p. 1262-1267.

Research output: Contribution to journalArticle

Horslen, SP, McCowan, TC, Goertzen, TC, Warkentin, PI, Cai, HB, Strom, SC & Fox, IJ 2003, 'Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder', Pediatrics, vol. 111, no. 6 I, pp. 1262-1267. https://doi.org/10.1542/peds.111.6.1262
Horslen, Simon P. ; McCowan, Timothy C. ; Goertzen, Timothy C. ; Warkentin, Phyllis Irene ; Cai, Hung Bo ; Strom, Stephen C. ; Fox, Ira J. / Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. In: Pediatrics. 2003 ; Vol. 111, No. 6 I. pp. 1262-1267.
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abstract = "Objective. Transplantation of isolated hepatocytes in animal models has been shown to correct inborn errors of metabolism. Based on these studies and our experience with hepatocyte transplantation in a child with Crigler-Najjar syndrome, isolated hepatocyte transplantation was performed to attempt metabolic reconstitution in a male infant with severe ornithine transcarbamylase (OTC) deficiency. Methods. An infant with an antenatal diagnosis of OTC deficiency was managed intensively to prevent hyperammonemia. Isolated hepatocytes were obtained by collagenase perfusion of donated livers not used for transplantation. Hepatocytes were infused in batches over the first 4 weeks of life via an umbilical venous catheter positioned in the portal vein. Immunosuppression consisted of tacrolimus and corticosteroids. Results. Over 4 billion viable hepatocytes were transplanted during the first 3.5 weeks of life. A period of metabolic stability was achieved between days 20 and 31 during which normal protein intake was tolerated while phenylbutyrate was weaned. During this time, plasma ammonia and glutamine remained within normal limits. Hyperammonemia reappeared abruptly on day 31 of life. Protein tolerance diminished to baseline; metabolic stability was subsequently reattained only following successful liver transplantation at 6 months of age. Conclusions. Isolated hepatocyte transplantation appeared to result in temporary relief of hyperammonemia and protein intolerance attributable to OTC deficiency. The metabolic stability achieved was lost after 11 days presumably because of rejection of the transplanted cells because of insufficient immunosuppression. Future attempts at isolated hepatocyte transplantation for inborn errors of metabolism in humans should include adequate immunosuppression and a liver biopsy as a means of proving hepatocyte engraftment and function.",
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AU - Strom, Stephen C.

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