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Orthotopic liver transplantation for Crigler-Najjar type I disease in six children
E M Sokal1, E S Silva, D Hermans
1Department of Pediatrics and Pediatric Surgery, St Luc Hospital, Catholic University of Louvain, Brussels, Belgium.
Insights
Orthotopic liver transplantation (OLT) cures severe hyperbilirubinemia in Crigler-Najjar disease type I (CN). Early OLT is crucial to prevent permanent neurological damage from kernicterus, offering excellent survival prospects.
Area of Science:
- Hepatology
- Genetics
- Pediatric Surgery
Background:
- Crigler-Najjar disease type I (CN) causes severe hyperbilirubinemia, posing a permanent risk of kernicterus (brain damage).
- Phototherapy offers partial control but does not eliminate the risk of neurological sequelae.
- Liver transplantation is the only curative option for this metabolic disorder.
Purpose of the Study:
- To evaluate the efficacy and outcomes of orthotopic liver transplantation (OLT) in patients with Crigler-Najjar disease type I.
- To assess the impact of OLT on hyperbilirubinemia and neurological status.
- To determine the long-term survival and quality of life post-transplantation.
Main Methods:
- Six patients with Crigler-Najjar disease type I underwent orthotopic liver transplantation (OLT).
- Patient data including age at surgery, pre- and post-transplant bilirubin levels, liver enzymes, and complications were analyzed.
- Follow-up assessments included serum bilirubin, liver function tests, neurological status, and overall quality of life.
Main Results:
- All six patients survived OLT with normalized serum bilirubin levels.
- Post-transplant follow-up ranged from 6 to 116 months.
- Three patients experienced post-OLT complications: tuberculosis, graft rejection/retransplantation, and hepatic artery thrombosis.
- Four patients achieved normal liver enzymes and integrated into normal education and social activities.
- One patient has ongoing neurological delay due to pre-transplant kernicterus.
- One patient developed chronic persistent hepatitis post-transplant.
Conclusions:
- Orthotopic liver transplantation (OLT) effectively cures hyperbilirubinemia in Crigler-Najjar disease type I.
- Early OLT before neurological sequelae develop is recommended for optimal outcomes.
- While OLT improves survival, pre-existing kernicterus can lead to persistent neurological deficits.
Abstract:
Hyperbilirubinemia in Crigler-Najjar disease type I (CN) can be partially controlled by daily phototherapy, but these children remain at permanent risk of developing brain damage due to kernicterus. Because liver transplantation is the only available curative treatment for liver-based inborn errors of metabolism, orthotopic liver transplantation (OLT) was performed in six patients with CN. Mean age at surgery was 52.5 months (range 27 to 100). Despite a mean daily phototherapy of 12.4 +/- 0.8 hr, mean bilirubin of the 6 patients was 388 microM/L (range 175 to 703) before OLT; one of them was also being treated with tin-protoporphyrin. All 6 had elevated AST/ALT, ranging from 1.4 to 6 times upper normal values. Complications occurred in three patients after OLT, including miliary tuberculosis in one, graft rejection and retransplantation in one, and hepatic artery thrombosis in one. All patients survive with normal serum bilirubin level (follow up 6 to 116 months). Four have normal enzymes on post-OLT follow-up (30 to 95 months), follow a normal education program, and have a normal social life. One recently transplanted patient has progressively normalizing liver function tests 6 months after OLT. One patient transplanted at 8 y.o. (now 116 months post-OLT) has moderate neurological delay due to pretransplant kernicterus, and posttransplant chronic persistent hepatitis. Our series shows that OLT cures hyperbilirubinemia in CN patients, with an excellent survival prospect. The procedure should be decided upon before neurological sequelae occur, since these persist after transplantation.