Guthery Stephen L, Heubi James E, Bucuvalas John C, Gross Thomas G, Ryckman Frederick C, Alonso Maria H, Balistreri William F, Hornung Richard W
Pediatric Liver Care Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Transplantation. 2003 Apr 15;75(7):987-93. doi: 10.1097/01.TP.0000057244.03192.BD.
Previous studies have suggested an increased risk of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (EBV-PTLD) in patients receiving tacrolimus for immunosuppression. We hypothesized that after correction for confounding variables, immunosuppression with tacrolimus is not associated with an increased risk of EBV-PTLD.
Potential cases of EBV-PTLD, identified by chart review, were independently ascertained by three clinicians and defined using published criteria. Agreement in diagnosing EBV-PTLD was measured using Kappa coefficients. Unadjusted and adjusted relative risk estimates were determined using proportional hazards regression.
Twenty-three cases of EBV-PTLD were identified in 221 patients, a proportion of 10.4% (95% confidence interval [CI]: 6.4%-14.4%). Multivariable analysis revealed that immunosuppression with tacrolimus was associated with an increased risk of EBV-PTLD (relative risk 3.10: 95% CI: 1.21-7.92), as was age at transplantation as a continuous variable (parameter estimate -0.15, P=0.03). Kappa coefficients in diagnosing EBV-PTLD and subclassifying as neoplastic and non-neoplastic EBV-PTLD were 0.73 (95% CI: 0.54-0.93) and 0.54 (95% CI: 0.40-0.68), respectively. Patients with neoplastic PTLD demonstrated a lower probability of survival than patients with non-neoplastic PTLD and non-cases.
Immunosuppression with tacrolimus and young age at transplantation are associated with an increased risk of EBV-PTLD in children undergoing liver transplantation, although we cannot exclude detection bias as an explanation for this observed increase. Good agreement between observers can be achieved using previously published criteria for defining EBV-PTLD. Patients with neoplastic EBV-PTLD may have a worse prognosis, and thus identification of risk factors for the development of this subtype of the disorder may be more important.
既往研究提示，接受他克莫司免疫抑制治疗的患者发生爱泼斯坦-巴尔病毒相关移植后淋巴增殖性疾病（EBV-PTLD）的风险增加。我们推测，在校正混杂变量后，他克莫司免疫抑制与EBV-PTLD风险增加无关。
通过病历审查确定的潜在EBV-PTLD病例由三名临床医生独立判定，并根据已发表的标准进行定义。使用卡帕系数衡量EBV-PTLD诊断的一致性。使用比例风险回归确定未调整和调整后的相对风险估计值。
在221例患者中确定了23例EBV-PTLD病例，比例为10.4%（95%置信区间[CI]：6.4%-14.4%）。多变量分析显示，他克莫司免疫抑制与EBV-PTLD风险增加相关（相对风险3.10：95%CI：1.21-7.92），移植时年龄作为连续变量也与风险增加相关（参数估计值-0.15，P=0.03）。EBV-PTLD诊断及分为肿瘤性和非肿瘤性EBV-PTLD的卡帕系数分别为0.73（95%CI：0.54-0.93）和0.54（95%CI：0.40-0.68）。肿瘤性PTLD患者的生存概率低于非肿瘤性PTLD患者和非病例患者。
接受肝移植的儿童使用他克莫司免疫抑制及移植时年龄较小与EBV-PTLD风险增加相关，尽管我们不能排除检测偏倚作为观察到的这种增加的解释。使用先前发表的定义EBV-PTLD的标准可在观察者之间达成良好的一致性。肿瘤性EBV-PTLD患者的预后可能更差，因此识别该疾病亚型发生的危险因素可能更为重要。
