Otte Jean-Bernard
Department of Pediatric Surgery and Liver Transplantation, Cliniques Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
Liver Transpl. 2016 Sep;22(9):1284-94. doi: 10.1002/lt.24470.
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. Liver Transplantation 22 1284-1294 2016 AASLD.
本综述展示了作者对小儿肝移植(LT)的起步、发展、现状及遗留问题的个人观点和贡献。世界各地无数接受肝移植的儿童已长大成人。技术已臻成熟。从我所在团队的经验来看,活体供者捐献的移植物可能会带来最佳的短期和长期效果。尽管他克莫司的地位无可撼动,但关于最佳免疫抑制(IS)的争论仍在继续。旨在诱导微嵌合体的耐受诱导方案已在临床移植中尝试,但未取得令人信服的结果。对于一些临床状态良好且肝功能检查正常的肝移植患儿,停用维持性免疫抑制是可行的,但这并非没有排斥风险以及随后组织学恶化的风险。布鲁塞尔团队目前倾向的趋势是在移植后尽快将免疫抑制降至最低,目标是达到“接近”或“几乎”耐受的状态。长期来看,肝移植物受到与肝炎相关的纤维化加剧的威胁,这很可能是免疫攻击所致。如今,重点在于长期生存、生活质量(生长、学业表现、就业、自我实现、生育、组建家庭等)、诱导耐受、预防与数十年免疫抑制相关的风险(肾毒性和神经毒性、心血管风险、新发恶性肿瘤等)以及预防移植物纤维化。所有这些问题都是年轻科学家的肥沃研究领域。《肝脏移植》2016年第22卷,第1284 - 1294页,美国肝病研究学会