Jain Ashok, Mazariegos George, Kashyap Randeep, Kosmach-Park Beverly, Starzl T E, Fung John, Reyes Jorge
Department of Surgery, Thomas E. Starzl Transplantation Institute, Children's Hospital of Pittsburgh, Pennsylvania 15213, USA.
Transplantation. 2002 Mar 27;73(6):941-7. doi: 10.1097/00007890-200203270-00020.
Survival after liver transplantation has improved significantly over the last decade with pediatric recipients faring better than adults. The 20-year experience of pediatric liver transplantation at Children's Hospital of Pittsburgh is reported in terms of patient survival; graft survival in relation to age, gender, and immunosuppressive protocols; causes of death; and indications for retransplantation.
From March 1981 to April 1998, 808 children received liver transplants at Children's Hospital of Pittsburgh. All patients were followed until March 2001, with a mean follow-up of 12.2+/-3.9 years (median=12.6; range=2.9-20). There were 405 female (50.2%) and 403 male (49.8%) pediatric recipients. Mean age at transplant was 5.3+/-4.9 years (mean=3.3; range 0.04-17.95), with 285 children (25.3%) being less than 2 years of age at transplant. Cyclosporine (CsA)-based immunosuppression was used before November 1989 in 482 children (50.7%), and the subsequent 326 recipients (40.3%) were treated with tacrolimus-based immunosuppression. Actuarial survival was calculated using the Kaplan-Meier statistical method. Differences in survival were calculated by log-rank analysis.
Overall patient survival at 1, 5, 10, 15, and 20 years was 77.1%, 72.6%, 69.4%, 65.8%, and 64.4%, respectively. There was no difference in survival for male or female patients at any time point. At up to 10 years posttransplant, the survival for children greater than 2 years of age (79.5%, 75.7%, and 71.6% at 1, 5, and 10 years, respectively) was slightly higher than those at less than 2 years of age (72.6%, 66.9%, and 65.3% at 1, 5, and 10 years, respectively). However, at 15 and 20 years posttransplant, survival rates were similar (>2 years=67.3% and 65.8%; <2 years=64.1% and 64.1%). A significant difference in survival was seen in CsA-based immunosuppression (71.2%, 68.1%, 65.4%, and 61%) versus tacrolimus-based immunosuppression (85.8%, 84.7%, 83.3%, and 82.9%) at 1, 3, 5, and 10 years, respectively (P=0.0001). The maximum difference in survival was noted in the first 3 months between CsA and tacrolimus; thus, indicating there may have been other factors (nonimmunological factors) involved in terms of donor and recipient selection and technical issues. The mean annual death rate beyond 2 years posttransplant was 0.47%, with the mean annual death rate for patients who received tacrolimus-based immunosuppression being significantly lower than those who received CsA-based immunosuppression (0.14% vs. 0.8%; P=0.001). The most common etiologies of graft loss were hepatic artery thrombosis (33.4%), acute or chronic rejection (26.6%), and primary nonfunction (16.7%). Of note, retransplantation for graft loss because of acute or chronic rejection occurred only in those patients who received CsA-based immuno-suppression.
The overall 20-year actuarial survival for pediatric liver transplantation is 64%. Survival has increased by 20% in the last 12 years with tacrolimus-based immunosuppression. Although this improvement may be the result of several factors, retransplantation as a result of acute or chronic rejection has been completely eliminated in patients treated with tacrolimus.
在过去十年中，肝移植后的生存率显著提高，小儿受者的情况优于成人。本文报告了匹兹堡儿童医院小儿肝移植20年的经验，内容包括患者生存率；与年龄、性别和免疫抑制方案相关的移植物生存率；死亡原因；以及再次移植的指征。
1981年3月至1998年4月，808名儿童在匹兹堡儿童医院接受了肝移植。所有患者均随访至2001年3月，平均随访时间为12.2±3.9年（中位数=12.6；范围=2.9 - 20）。小儿受者中，女性405名（50.2%），男性403名（49.8%）。移植时的平均年龄为5.3±4.9岁（中位数=3.3；范围0.04 - 17.95），其中285名儿童（25.3%）移植时年龄小于2岁。1989年11月前，482名儿童（50.7%）采用基于环孢素（CsA）的免疫抑制治疗，随后的326名受者（40.3%）采用基于他克莫司的免疫抑制治疗。采用Kaplan-Meier统计方法计算精算生存率。通过对数秩分析计算生存率的差异。
1年、5年、10年、15年和20年的总体患者生存率分别为77.1%、72.6%、69.4%、65.8%和64.4%。在任何时间点，男性或女性患者的生存率均无差异。移植后10年内，年龄大于2岁儿童的生存率（1年、5年和10年分别为79.5%、75.7%和71.6%）略高于年龄小于2岁的儿童（1年、5年和10年分别为72.6%、66.9%和65.3%）。然而，移植后15年和20年时，生存率相似（>2岁=67.3%和65.8%；<2岁=64.1%和64.1%）。基于CsA的免疫抑制治疗在1年、3年、5年和10年时的生存率分别为71.2%、68.1%、65.4%和61%，与基于他克莫司的免疫抑制治疗（分别为85.8%、84.7%、83.3%和82.9%）相比，存在显著差异（P = 0.0001）。CsA和他克莫司在生存方面的最大差异出现在前3个月；因此，表明在供体和受体选择以及技术问题方面可能涉及其他因素（非免疫因素）。移植后2年以上的平均年死亡率为0.47%，接受基于他克莫司免疫抑制治疗的患者平均年死亡率显著低于接受基于CsA免疫抑制治疗的患者（0.14%对0.8%；P = 0.001）。移植物丢失的最常见病因是肝动脉血栓形成（33.4%）、急性或慢性排斥反应（26.6%）和原发性无功能（16.7%）。值得注意的是，因急性或慢性排斥反应导致移植物丢失而进行再次移植仅发生在接受基于CsA免疫抑制治疗的患者中。
小儿肝移植20年的总体精算生存率为64%。在过去12年中，基于他克莫司的免疫抑制治疗使生存率提高了20%。尽管这种改善可能是多种因素的结果，但在接受他克莫司治疗的患者中，因急性或慢性排斥反应导致的再次移植已完全消除。
