Pediatric liver transplantation for urea cycle disorders and organic acidemias: United Network for Organ Sharing data for 2002‐2012

Abstract

Background Decision-making about liver transplant is unique in children with urea cycle disorders (UCD) and organic acidemias (OA) because of immediate high priority on the waiting list, not related to severity of disease. There is limited national outcomes data on which to base recommendations about liver transplant for UCD or OA. Methods Retrospective analysis of UNOS data on liver recipients <18 years, transplanted 2002–12. Repeat transplants excluded. Results 5.4% of pediatric liver transplants were liver-only for UCD/OA. UCD/OA increased from 4.3% of transplants in 2002–05 to 7.4% in 2010–12 (p<0.0001). 96% were deceased donor. Of these, 59% were transplanted at <2 years of age. Graft survival improved as age at transplant increased (p=0.04). By 5 years post-transplant, graft survival was 78% for children <2 years at transplant and 88% for those ≥2 years (p=0.06). Vascular thrombosis caused 45% of graft losses; 65% in children <2 years. Patient survival also improved as age at transplant increased; 5-year patient survival was 88% in UCD/OA children <2 years at transplant and 99% in those ≥2 years (p=0.006). At last-follow up (54 ± 34.4 months), children transplanted for UCD/OA were more likely to have cognitive and motor delay than those transplanted for other indications. Cognitive and motor delay in UCD/OA children were associated with metabolic disorder but not predicted by age or weight at transplant, gender, ethnicity, split vs. whole liver, or hospitalization at transplant in univariate and multivariate analysis. Conclusion Most liver transplants for UCD/OA occur in early childhood. Further research is needed on the benefits of early transplant for UCD/OA, as younger age may increase post-transplant morbidity.

Early Liver Transplantation for Neonatal-Onset Methylmalonic Acidemia

“…23 Recent data suggest that children with organic acidemia and hyperammonemia undergoing transplant at the youngest ages have the highest risk of graft loss, which is often related to technical difficulties during surgery. 24 However, the reported increased morbidity in younger children should be considered carefully, given the limited experience of some centers with liver transplants in very small children, potentially contributing to suboptimal results. 25 Additionally, children with these rare conditions are looked after by tertiary specialists in metabolic units, often with no direct links to the transplant centers, so that the patients are proposed for liver transplant when the margins for recuperation are limited.…”

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“…3 However, the United Network for Organ Sharing data have suggested that patients at the youngest ages appear to have the highest graft morbidity due to difficult vascular anastomoses and consequent thrombosis. 4 Our 6.5-year-old patient (who received a liver transplant at the age of 2 years) had hepatic artery thrombosis, which was treated with angiography, intra-arterial tissue plasminogen activator infusion, and subsequent hepatic artery reanastomosis. The optimal timing of liver transplant for young patients remains unclear.…”

“…3 As shown in several studies, 5-year survival rates are greater than 85% with transplant. [4][5][6] Liver transplant during the first few months of life may prevent neurologic deficits in severe cases. However, transplant at early ages also may increase the risk of perioperative and postoperative complications.…”

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“…Argininosuccinic aciduria is the only urea cycle disorder in which liver fibrosis can develop as a late complication. 5,6,8,9 The number of cases in which LT has been performed for urea cycle disorders is limited.…”