Rodríguez-Perálvarez Manuel, De Luca Laura, Crespo Gonzalo, Rubin Ángel, Marín Sandra, Benlloch Salvador, Colmenero Jordi, Berenguer Marina, Navasa Miguel, Tsochatzis Emmanuel, De la Mata Manuel
Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain.
UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK.
Clin Transplant. 2017 Jul;31(7). doi: 10.1111/ctr.13005. Epub 2017 Jun 10.
A uniform definition of clinical suspicion of T-cell-mediated rejection (TCMR) in liver transplantation (LT) is needed to homogenize clinical decisions, especially within randomized trials. This multicenter study included a total of 470 primary LT recipients. The derivation cohort consisted of 142 patients who had clinically driven liver biopsies at any time after LT. The external validation cohort included 328 patients who underwent protocol biopsies at day 7-10 after LT. The rates of moderate-severe histological TCMR were 33.8% in the derivation cohort and 43.6% in the validation cohort. Independent predictors (ie, risk factors) of moderate-severe TCMR in the derivation cohort were as follows: serum bilirubin >4 mg/dL (OR=5.83; P<.001), rising bilirubin within the 4 days prior to liver biopsy (OR=4.57; P=.003), and blood eosinophils count >0.1×10 /L (OR=3.81; P=.004). In the validation cohort, the number of risk factors was an independent predictor of moderate-severe TCMR (OR=1.74; P=.001), after controlling for hepatitis C status. The number of risk factors paralleled the rates of moderate-severe TCMR in the derivation and validation cohorts (P<.001 in both comparisons). In conclusion, increased serum bilirubin, rising bilirubin and eosinophilia are validated risk factors for moderate-severe histological TCMR and could be used as objective criteria to select candidates for liver biopsy.
肝移植（LT）中需要对T细胞介导的排斥反应（TCMR）的临床怀疑有统一的定义，以使临床决策同质化，尤其是在随机试验中。这项多中心研究共纳入了470例初次LT受者。推导队列由142例LT后任何时间进行临床驱动肝活检的患者组成。外部验证队列包括328例LT后第7 - 10天接受方案活检的患者。推导队列中中度至重度组织学TCMR的发生率为33.8%，验证队列中为43.6%。推导队列中中度至重度TCMR的独立预测因素（即危险因素）如下：血清胆红素>4 mg/dL（OR = 5.83；P <.001）、肝活检前4天内胆红素升高（OR = 4.57；P =.003）以及血液嗜酸性粒细胞计数>0.1×10⁹/L（OR = 3.81；P =.004）。在验证队列中，在控制丙型肝炎状态后，危险因素的数量是中度至重度TCMR的独立预测因素（OR = 1.74；P =.001）。危险因素的数量与推导队列和验证队列中中度至重度TCMR的发生率平行（两项比较中P均<.001）。总之，血清胆红素升高、胆红素升高和嗜酸性粒细胞增多是中度至重度组织学TCMR的经验证的危险因素，可作为选择肝活检候选者的客观标准。
