Isolated Hepatocyte Transplantation for Crigler-Najjar Syndrome Type 1
Crigler-Najjar syndrome type 1 (CN1) is an inherited disorder characterized by the absence of hepatic uridine diphosphoglucuronate glucuronosyltransferase (UDPGT), the enzyme responsible for the conjugation and excretion of bilirubin. We performed allogenic hepatocyte transplantation
(AHT) in a child with CN1, aiming to improve bilirubin glucuronidation in this condition. A 9-year-old boy with CN1 was prepared with plasmapheresis and immunosuppression with prednisolone and tacrolimus. When a graft was made available, 7.5 × 109 hepatocytes were isolated
and infused into the portal vein percutaneously. After 2 weeks phenobarbitone was added to promote the enzymatic activity of UDPGT of the transplanted hepatocytes. Nocturnal phototherapy was continued throughout the studied period. Total bilirubin was considered a reliable marker of allogenic
cell function. There was no significant variation of vital signs nor complications during the infusion. Mean ± SD bilirubin level was 530 ± 38 μmol/L before and 359 ± 46 μmol/L after AHT (t-test, p < 0.001). However, the introduction of phenobarbitone
was followed by a drop of tacrolimus level with increase of alanine aminotransferase (ALT) and increase of bilirubin. After standard treatment of cellular rejection bilirubin fell again but from then on it was maintained at a greater level. After discharge the patient experienced a further
increase of bilirubin that returned to predischarge levels after readmission to the hospital. This was interpreted as poor compliance with phototherapy. Only partial correction of clinical jaundice and the poor tolerability to nocturnal phototherapy led the parents to refuse further hepatocyte
infusions and request an orthotopic liver transplant. After 24 months the child is well, with good liver function on tacrolimus and prednisolone-based immunosuppression. Isolated AHT, though effective and safe, is not sufficient to correct CN1. Maintenance of adequate immunosuppression and
family compliance are the main factors hampering the success of this procedure.
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Enzyme replacement therapy;
Uridine diphosphoglucuronate glucuronosyltransferase
Document Type: Review Article
Department of Surgery and Gastroenterological Science, University of Padova, Padova, Italy
Department of Pathology, University of Pittsburgh, Pittsburgh, PA
Department of Paediatrics, University of Padova, Padova, Italy
Department of Laboratory Medicine, University of Padova, Padova, Italy
Department of Radiology, University of Padova, Padova, Italy
Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy
Department of Pathology, University of Padova, Padova, Italy
Publication date: 01 February 2005
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