PubMed2002
The history of pediatric liver transplantation cannot be dissociated from one man, Thomas E. Starzl, whose pioneer efforts contributed more than anyone else to what has become a routinely successful clinical procedure. During the pre-cyclosporine era, the pediatric experience was confined nearly exclusively in Denver: first attempt in 1963, first success with survival beyond one year in 1967, cumulative experience with 84 pediatric cases in the pre-cyclosporine era (1967-1979) with a 2-year patient survival rate of 30%. The stampede for the development of other liver transplant centers came with the introduction of cyclosporine in the early eighties. Besides Pittsburgh, seven centers (Brussels, Cambridge and Hanover in Europe; Boston, Dallas, UCLA, Minneapolis in USA) had performed up to 1986 at least 20 pediatric liver transplants each with a long-term (>1 year) patient survival rate ranging between 57% and 83%. At the moment, a long-term patient survival rate in excess of 90% in elective patients -including infants - is commonly obtained in experienced centers. The shortage of size matched liver donors which was responsible for a high death rate on the cadaveric waiting list stimulated the development or technical innovations based on the segmental anatomy of the liver: reduced ('cutdown') liver graft, split graft and living liver transplantation. Challenging technical aspects in the recipient have been solved in order to reduce the incidence of surgical complications like outflow obstruction, arterial and portal thrombosis, and biliary problems. The indications of liver transplantation have been refined; regarding biliary atresia, which is the most frequent indication, a consensus has developed to propose a sequential strategy with a single attempt at hepatoportoenterostomy followed, when it fails, by liver transplantation. Some contra-indications accepted in the past are not currently valid with better understanding of the pathophysiology and/or increased clinical experience; such is the case of the hepatopulmonary syndrome. A major progress in preoperative management has been achieved through a multidisciplinary approach, particularly regarding nutrition and control of portal hypertension-related bleeding and ascites. Perioperatively, liver transplantation has derived benefit from the expertise of anesthetists managing babies with serious conditions and increased experience of the transplant surgeons regarding the knowledge of all the technical modalities, good strategy, technical skills and meticulous control of bleeding. It is well-recognized that children require more immunosuppression than adults. As in adults, the first breakthrough came with the introduction of cyclosporine which more than doubled the one-year patient survival rate. The next advance during the last decade was afforded by FK 506 - Tacrolimus which allows steroid withdrawal with the first year post-transplant in most patients. Besides its efficacy in reducing the incidence of rejection and absence of cosmetic side-effects, the steroid-sparing effect of Tacrolimus is of utmost importance to preserve the growth potential of children. The use of OKT-3 both for induction and treatment of rejection has been abandoned nearly universally because its use, cumulated with other immunosuppressants, resulted in a high incidence of lymphoproliferative disorder. In contrast, anti-IL2-receptor monoclonal antibodies, will most likely gain an increasing place in induction, with the availability of chimeric or humanized preparations. The side-effects of immunosuppression can endanger both the quality of life and the life expectancy; they are a special source of concern in pediatric recipients whose survival can be expected to be more than a few decades. Children would benefit most from the development of a marker able to identify the patients who have developed graft acceptance, allowing complete wearing of immunosuppression. Also they would benefit most from research protocols of tolerance induction. Since the vast majority of liver-transplanted children will have a reasonably normal life expectancy, the focus should be switched to their long-term rehabilitation and the assessment of their quality of life when they reach adulthood.