Schlitt H J, Nashan B, Krick P, Ringe B, Wittekind C, Wonigeit K, Pichlmayr R
Klinik für Abdominal-und Transplantationschirurgie, Medizinische Hochschule Hannover, Germany.
Transplantation. 1992 Aug;54(2):273-8. doi: 10.1097/00007890-199208000-00016.
Evaluation of graft morphology is regarded as a cornerstone for diagnosis of acute liver graft rejection. Here we have studied the clinical relevance of biopsy findings obtained either by aspiration cytology or by histology in the first month after human liver transplantation, and have assessed the influence of immunosuppressive induction treatment on the incidence of morphological and clinical rejection. Results of 865 aspiration biopsies (TAC) and 155 core biopsies in 141 patients were correlated with the retrospective clinical diagnosis concerning the presence or absence of acute rejection. This analysis demonstrated that there are almost no false negative findings either in cytology or in histology (less than 0.1% of negative biopsies). In contrast, with both methods a large number of positive biopsy results were obtained that were without clinical correlate ("false positive" biopsies; 46% and 41% of positive cytologies and histologies, respectively). The rates of clinical and morphological acute rejections were differently influenced by the type of immunosuppressive induction protocol used. The incidence of clinical rejection was particularly low with a quadruple drug regimen when cyclosporine therapy was started immediately after transplantation (29% vs. 62% when introduction of cyclosporine was delayed for 2-5 days). Morphological rejections were similarly frequent with immediate and delayed introduction of cyclosporine at 2 mg/kg during quadruple therapy (65-75%) and were only reduced with initial high dose cyclosporine treatment (5 mg/kg) (35%). Antirejection treatment was not required in patients with morphological evidence of rejection but without clinical symptoms. The study demonstrates that cytology and histology are similarly reliable for exclusion and similarly unreliable for diagnosis of clinical acute rejection. The clinical relevance of positive biopsy findings is strongly influenced by the basic immunosuppressive treatment. Certain types of induction treatment can obviously alter the alloresponse in a way that no graft damage occurs despite the presence of marked intragraft immune activation. "False-positive" biopsy findings, therefore, seem to represent a qualitatively modified and self-limited type of intragraft alloresponse that is without clinical consequences ("incomplete" or "subclinical" rejection).
移植肝形态学评估被视为诊断急性肝移植排斥反应的基石。在此，我们研究了人类肝移植术后第一个月通过细针穿刺细胞学检查或组织学检查所获活检结果的临床相关性，并评估了免疫抑制诱导治疗对形态学和临床排斥反应发生率的影响。对141例患者的865次细针穿刺活检（TAC）和155次组织芯活检结果与关于急性排斥反应有无的回顾性临床诊断进行了相关性分析。该分析表明，细胞学检查和组织学检查几乎均无假阴性结果（阴性活检不到0.1%）。相比之下，两种方法均获得了大量无临床相关性的阳性活检结果（“假阳性”活检；分别占阳性细胞学检查和组织学检查的46%和41%）。所采用的免疫抑制诱导方案类型对临床和形态学急性排斥反应发生率的影响不同。当移植后立即开始环孢素治疗时，四联药物方案的临床排斥反应发生率特别低（29%，而环孢素延迟2 - 5天引入时为62%）。在四联治疗期间，环孢素立即或延迟以2 mg/kg引入时，形态学排斥反应同样常见（65 - 75%），仅在初始高剂量环孢素治疗（5 mg/kg）时有所降低（35%）。有形态学排斥反应证据但无临床症状的患者无需进行抗排斥治疗。该研究表明，细胞学检查和组织学检查在排除临床急性排斥反应方面同样可靠，而在诊断方面同样不可靠。阳性活检结果的临床相关性受基础免疫抑制治疗的强烈影响。某些类型的诱导治疗显然可以改变同种异体反应，使得尽管移植肝内存在明显的免疫激活，但未发生移植肝损伤。因此，“假阳性”活检结果似乎代表了一种性质改变且自我限制的移植肝内同种异体反应类型，无临床后果（“不完全”或“亚临床”排斥反应）。
