Isolated Hepatocyte Transplantation in an Infant With a Severe Urea Cycle Disorder

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 trans- plantation was performed to attempt metabolic reconsti- tution in a male infant with severe ornithine transcar- bamylase (OTC) deficiency. Methods. An infant with an antenatal diagnosis of OTC deficiency was managed intensively to prevent hy- perammonemia. 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. Immunosuppres- sion consisted of tacrolimus and corticosteroids. Results. Over 4 billion viable hepatocytes were trans- planted 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 sta- bility was subsequently reattained only following suc- cessful liver transplantation at 6 months of age. Conclusions. Isolated hepatocyte transplantation ap- peared 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 at- tempts 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. Pediatrics 2003;111:1262-1267; hepatocyte transplantation, infant, ornthine transcarbamylase deficiency, urea cycle disorder.