Brunner-La Rocca H P, Sütsch G, Schneider J, Follath F, Kiowski W
Division of Cardiology, University Hospital, Zurich, Switzerland.
Circulation. 1996 Sep 15;94(6):1334-8. doi: 10.1161/01.cir.94.6.1334.
The significance of International Society for Heart Transplantation (ISHT) grade 2 cardiac allograft rejection has been questioned, and the medical community is not in complete agreement as to its clinical management. We therefore retrospectively analyzed the follow-up of all available endomyocardial biopsy samples obtained from 161 transplant patients since introduction of the ISHT nomenclature at our institution.
Of 2868 biopsies performed 3 days to 8.9 years after transplantation, 420 biopsies had no follow-up or were preceded by intensified immunosuppression and were excluded from analysis. Of the remaining 2448 biopsies, 374 (15.3%) were repeat biopsies performed 7 to 10 days after prior ISHT 2 rejection without change of treatment. Of these, 70 (18.7%) had progressed to > or = ISHT 3A, whereas 82 (21.9%) remained unchanged and 222 (59.4%) resolved. In contrast, follow-up of 2074 biopsies with lower-grade rejection showed graft rejection classified as > or = ISHT 3A in 153 (7.4%), ISHT 2 in 240 (11.6%), and < or = ISHT 1B in 1681 (81.1%) biopsy samples (P < .0001). In univariate analysis, the odds ratio (OR) of graft rejection > or = ISHT 3A after ISHT 2 rejection was 2.89. Other univariate predictors of rejection > or = ISHT 3A were time after transplantation (OR = 0.96 per month, P < .0001), blood group type B (OR = 1.62, P < .005), "Quilty" lesion on previous biopsy (OR = 1.70, P < .005), number of HLA mismatches (OR = 1.27 per mismatch, P < .005), female sex (OR = 1.55, P < .05), and serum creatinine level (OR = 0.93 per 10 mumol/L, P < .005). Young age of recipients was a risk factor during long-term (> or = 2 years) follow-up (P < .002), and lower cyclosporine level was a risk factor during the first month after transplantation (P < .01). In multivariate logistic regression analysis, ISHT 2 rejection on previous biopsy remained the strongest predictor of rejection > or = ISHT 3A (OR = 2.40, P < .0001).
Several factors independently increase the risk of rejection classified as > or = ISHT 3A. The strongest predictor of a grade of > or = ISHT 3A was ISHT 2 rejection on the previous biopsy obtained 7 to 10 days earlier. Therefore, ISHT 2 graft rejection is of clinical significance, and short-term follow-up appears to be warranted even late after transplantation.
国际心脏移植学会（ISHT）2级心脏移植排斥反应的意义受到质疑，医学界对其临床管理尚未完全达成一致意见。因此，我们回顾性分析了自本院引入ISHT命名法以来，161例移植患者所有可用的心肌内膜活检样本的随访情况。
在移植后3天至8.9年进行的2868次活检中，420次活检没有随访或在之前有强化免疫抑制治疗，被排除在分析之外。在其余2448次活检中，374次（15.3%）是在之前ISHT 2级排斥反应后7至10天进行的重复活检，且治疗未改变。其中，70次（18.7%）进展为≥ISHT 3A，82次（21.9%）保持不变，222次（59.4%）得到缓解。相比之下，对2074次低级别排斥反应活检的随访显示，活检样本中移植排斥反应分类为≥ISHT 3A的有153次（7.4%），ISHT 2级的有240次（11.6%），≤ISHT 1B级的有1681次（81.1%）（P<.0001）。单因素分析中，ISHT 2级排斥反应后移植排斥反应≥ISHT 3A的比值比（OR）为2.89。排斥反应≥ISHT 3A的其他单因素预测因素包括移植后的时间（每月OR = 0.96，P<.0001）、B型血（OR = 1.62，P<.005）、之前活检出现“奎尔蒂”病变（OR = 1.70，P<.005）、HLA错配数（每一个错配OR = 1.27，P<.005）、女性（OR = 1.55，P<.05）以及血清肌酐水平（每10 μmol/L OR = 0.93，P<.005）。受者年轻是长期（≥2年）随访期间的一个危险因素（P<.002），而移植后第一个月环孢素水平较低是一个危险因素（P<.01）。在多因素逻辑回归分析中，之前活检出现ISHT 2级排斥反应仍然是排斥反应≥ISHT 3A的最强预测因素（OR = 2.40，P<.0001）。
有几个因素独立增加了分类为≥ISHT 3A的排斥反应风险。≥ISHT 3A级的最强预测因素是7至10天前进行的上一次活检出现ISHT 2级排斥反应。因此，ISHT 2级移植排斥反应具有临床意义，即使在移植后期似乎也有必要进行短期随访。
