Date: Tuesday 23rd September
Time: 12.30 – 1.30
Title: Liver transplantation for inherited metabolic disease
Speaker: Dr Patrick McKiernan,
Abstract: Liver transplantation is one of the outstanding successes of high technology medicine. Paediatric liver transplantation can now offer greater than 90% expectation of survival into adulthood with good quality of life. Since the introduction of liver transplantation, inherited metabolic disorder has been the indication in approximately 15% of cases.
These indications however are never static. In an individual child and family a decision must be made incorporating the likely success of transplantation, the impact of the metabolic defect on the child and the family, the natural history of the defect and whether any new therapies are available or imminent. As a result, inherited defects that may be a contraindication to transplantation in one era may be a definite indication in another and vice versa.
The indication for, and likely effect of, transplantation in individual defects can be predicted. The primary category is the presence/absence of significant liver disease and the secondary category is whether or not the metabolic defect is confined to the liver.
Where there is liver disease, the presence of a metabolic defect has minimal impact on the indication for transplant. Where there is no primary liver disease then transplant is indicated by the severity and impact of the metabolic defect. If transplantation is indicated it should not be unduly delayed and ideally should be undertaken before school age.
Where the defect is confined to the liver, transplantation results in complete correction and removes the risk of further neurological damage. Where the defect is extrahepatic there are likely to some residual disease. For example, in the organic acidaemias transplant results in significant disease amelioration with improved quality of life, albeit with a persistent need for metabolic treatment. Recent developments have transformed the impact of residual disease in Glycogen storage disease and progressive familial intrahepatic cholestasis Type 1.
Live Related Liver Transplantation. Most inherited metabolic diseases are autosomal recessive, hence parents are obligate heterozygoes. In most diseases this has no effect on either the risk to the parent or the efficacy of metabolic control in the recipient.
Recent advances have offered practical alternatives to transplantation for Tyrosinaemia type 1, atypical HUS, Hyperoxaluria type 1 and Cholesterol ester storage disease. Genetic therapy based approaches have rapidly expanded and have exciting potential to delay or prevent the need for transplant but remain experimental.