Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Liver Transpl. 2013 Jul;19(7):730-40. doi: 10.1002/lt.23659.
Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality in pediatric recipients of liver transplantation (LT).
Describe the incidence of PTLD and symptomatic Epstein-Barr virus (SEBV) disease in a large multicenter cohort of children who underwent LT with a focus on the risk factors and changes in incidence over time. SEBV and PTLD were prospectively determined in 2283 subjects who had undergone LT for the first time with at least 1 year of follow-up in the Studies of Pediatric Liver Transplantation database. SEBV was defined with specific criteria, and PTLD required tissue confirmation. The incidence of SEBV and PTLD was determined with a Kaplan-Meier analysis. Univariate and multivariate modeling of risk factors was performed with standard methods. SEBV occurred in 199 patients; 174 (87.4%) were EBV-negative at LT. Seventy-five patients developed PTLD, and 64 (85.3%) of these patients were EBV-negative at LT. Among the 2048 patients with at least 2 years of follow-up, 8.3% developed SEBV by the second year after LT, and 2.8% developed PTLD. There were lower rates of SEBV (5.9% versus 11.3%, P < 0.001) and PTLD (1.7% versus 4.2%, P = 0.001) in 2002-2007 versus 1995-2001. In 2002-2007, tacrolimus and cyclosporine trough blood levels in the first year after LT were significantly lower, and fewer children were receiving steroids. Biliary atresia, and recipient EBV status were correlated. In a multivariate analysis, era of LT, recipient EBV status, and frequent rejection episodes were associated with SEBV and PTLD. The incidence of SEBV and PTLD is decreasing in pediatric LT recipients concomitantly with a reduction in immunosuppression. Younger recipients and those with multiple rejections remain at higher risk for SEBV and PTLD.
描述在接受肝移植（LT）的儿童中，PTLD 和有症状 EBV 疾病（SEBV）的发病率，并重点关注随时间推移的发病率变化及其危险因素。对接受首次 LT 的 2283 名患者进行 SEBV 和 PTLD 的前瞻性检测，这些患者的随访时间至少为 1 年，数据来自于儿科肝移植研究数据库。SEBV 通过特定标准定义，PTLD 需要组织确认。通过 Kaplan-Meier 分析确定 SEBV 和 PTLD 的发病率。采用标准方法进行单变量和多变量危险因素建模。199 名患者发生 SEBV；174 名患者（87.4%）在 LT 时 EBV 阴性。75 名患者发生 PTLD，其中 64 名患者（85.3%）在 LT 时 EBV 阴性。在 2048 名至少随访 2 年的患者中，8.3%的患者在 LT 后第 2 年发生 SEBV，2.8%的患者发生 PTLD。与 1995-2001 年相比，2002-2007 年 SEBV（5.9%比 11.3%，P<0.001）和 PTLD（1.7%比 4.2%，P=0.001）的发生率更低。与 1995-2001 年相比，2002-2007 年 LT 时环孢素和他克莫司的血药浓度更低，接受皮质类固醇治疗的儿童更少。胆道闭锁和受者 EBV 状态相关。在多变量分析中，LT 时代、受者 EBV 状态和频繁的排斥反应与 SEBV 和 PTLD 相关。在接受 LT 的儿童中，SEBV 和 PTLD 的发病率正在降低，同时免疫抑制也在减少。年轻受者和多次排斥反应的受者仍然面临更高的 SEBV 和 PTLD 风险。
