Background:

Crigler-Najjar (CN) syndrome type I is a rare disorder of bilirubin metabolism caused by a deficiency of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). Patients are at risk of developing fatal brain injury due to unconjugated hyperbilirubinemia throughout life. Treatment consists of blood exchange transfusions in the neonatal period and 10 – 12h phototherapy daily thereafter. Most patients undergo orthotopic liver transplantation as phototherapy becomes less effective after puberty and constitutes a significant impairment in quality of life.

Case report:

A 13-year-old boy and an 11-year-old girl with CN syndrome type I were evaluated at our center. Clinical diagnosis had been confirmed in both patients by lack of conjugated bilirubin in bile and identification of a mutation in the UGT1A1 gene causing loss of function. Both patients required 8 – 12h of phototherapy to maintain serum bilirubin at 390 to 450 μmol per liter. After ethical committee approval and informed consent, patients were accepted to the waiting list for hepatocyte transplantation. Hepatocytes were isolated under good manufacturing practices from liver tissue obtained from deceased organ donors not accepted for whole organ transplantation or from split or size reduced liver transplantations. Fresh ABO compatible hepatocytes were infused by a portal catheter introduced through the umbilical or a mesenteric vein. Immediately before placement of the catheters patients underwent liver resection of segments 2 and 3 to induce liver regeneration and proliferation of transplanted hepatocytes. Immunosuppression consisted of basiliximab induction, tacrolimus and steroid pulse followed by tapering. The girl received 5.3 x 10⁹ viable hepatocytes at one transplantation event and the boy received two infusions from two different donors three months apart with 2.2 and 9 x 10⁹ viable hepatocytes. In both patients serum bilirubin levels increased initially after the first procedure up to 530 μmol per liter. Thereafter serum bilirubin decreased continuously in both patients to 50% of pre-transplant levels for more than 6 months. The boy experienced a sudden increase of serum bilirubin to pre-transplant levels 6 months after the first infusion associated with a scabies infection. Despite intensified phototherapy serum bilirubin did not improve. Due to the risk of encephalopathy we decided together with the family to list him for orthotopic liver transplantation. The girl still remains on significantly decreased serum bilirubin levels and is on the waiting list for further hepatocyte infusions.