Pediatric liver transplantation: Personal perspectives on historical achievements and future challenges

Abstract

This review presents the author's personal perspective and contributions to the first steps, the development, the current status, and the remaining issues of pediatric liver transplantation (LT). Innumerable children around the world who have undergone LT have reached adulthood. The techniques have reached maturity. As shown by my own group's experience, grafts donated by living donors might provide the best short-term and longterm results. Debate persists about the optimal immunosuppression (IS), although the place of tacrolimus remains unchallenged. Tolerance induction protocols aiming to induce microchimerism have been tried in clinical transplantation without convincing results. Withdrawal of maintenance IS is possible in some children who underwent liver transplantation who have excellent clinical status and normal liver function tests but is not without risk of rejection and subsequent worsening of histology. The current trend favored by the Brussels' group is to minimize IS as soon after transplant as possible, aiming to obtain a state of "prope" or "almost" tolerance. Liver grafts are threatened in the long term by increasing hepatitis-related fibrosis, resulting most likely from immunological assault. Nowadays, the focus is on the longterm survival, quality of life (growth, academic performance, employment, self-fulfillment, fertility, raising a family, etc.), induction of tolerance, prevention of risks bound to decades of IS (nephrotoxicity and neurotoxicity, cardiovascular risk, de novo malignancies, etc.), and prevention of graft fibrosis. All these issues are fertile fields for younger scientists.

Aggressive prevention and preemptive management of vascular complications after pediatric liver transplantation: A major impact on graft survival and long‐term outcome

“…It was close to a 98% actual patient survival over a 7‐year period—and with a minimum follow‐up of 2 years afterward for each graft. These results compare well with other series that have been published recently or even earlier . More interestingly, these results have suggested that the vast majority of surviving grafts have an excellent function at the very long‐term point, with fully normal liver tests in 78.7% of the patients.…”

Pharmacoepidemiology of tacrolimus in pediatric liver transplantation

“…Currently, immunosuppression in pediatric liver transplantation consists of multidrug therapy including induction therapy, low‐dose tacrolimus, steroids, sirolimus, and/or mycophenolate mofetil . The aim of the treatment is to avoid rejection but also to minimize renal dysfunction, PTLD, infection, hypertension, and hyperlipidemia .…”

Pediatric living donor liver transplantation: A single center experiences

“…Liver transplantation has become a standard procedure for children with end-stage liver disease [2]. The most common clinical indications for liver transplant in pediatric patients are cholestatic liver disease, which accounts for almost half of the patients; metabolic and genetic disorders; fulminant liver failure; and malignancies [3][4][5].…”