Liver transplantation in childhood--Clinical and experimental problems (author's transl)

Abstract

Liver transplantation represents an attempt to save the life of individual patients. During childhood the most important indications are the non-corrigible type of biliary duct atresia and cirrhoses due to chronic aggressive hepatitis and congenital metabolic errors. The donor problem is particularly serious in children because there are so few donors. Rejection processes in a transplanted liver are difficult to verify, necessitating diagnosis by exclusion of other functional disturbances of the liver. It seems that the rejection reaction is less violent and less frequent than is the case with other organs. Immunosuppressive therapy is required to cope with this phenomenon which has not been satisfactorily solved so far.Points of emphasis of experimental research in liver transplantation are: optimization of storage and preservation conditions; clarification of immunoresponse to an allogenic transplant and the use of suitable immunosuppressives. The authors used rats in model experiments designed to tackle these problems. The hypothermia required for preservation of the organ results in damaging the organ besides slowing down metabolic activity (the latter being of course a welcome effect); the organ damage is caused by the swelling of the cells, as well as, in the authors' opinion, by the unequal deceleration along important paths of intermediary metabolism. This could result in co-ordination disturbances of metabolism which would impair the vitality of preserved livers. Studies on immunoresponse were conducted by the authors with the help of the model of orthotopic liver transplantation. This model was standardized particularly by developing a suitable technique of bile duct reconstruction. Transplantations effected in 24 different donor-recipient combinations showed that the fate of transplanted livers depends on the individual combination of antigens and that extended survival times are not a general property common to liver transplants. It appears probable that the large spectrum of various survival times is representative of a ranking of the individual antigens in respect of their capacity to immunoresponse. The humoral immunoresponse to liver transplants is different in different pairings. Rejection of allogenic transplants can be prevented by administration of Cyclosporine A for the duration of one month.