Pinon Michele, Pizzol Antonio, Chiadò Cristina, David Ezio, Chiusa Luigi, Dell'Olio Dominic, Isolato Giuseppe, Amoroso Antonio, Deaglio Silvia, Catalano Silvia, Tandoi Francesco, Romagnoli Renato, Calvo Pier Luigi
Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy.
Pathology Unit, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy.
Transplantation. 2022 Jan 1;106(1):85-95. doi: 10.1097/TP.0000000000003649.
The impact of graft fibrosis and inflammation on the natural history of pediatric liver transplants is still debated. Our objectives were to evaluate the evolution of posttransplant fibrosis and inflammation over time at protocol liver biopsies (PLBs), risk factors for fibrosis, presence of donor-specific antibodies (DSAs), and/or their correlation with graft and recipient factors.
A single-center, retrospective (2000-2019) cross-sectional study on pediatric liver transplant recipients who had at least 1 PLB, followed by a longitudinal evaluation in those who had at least 2 PLBs, was conducted. Fibrosis was assessed by the Liver Allograft Fibrosis Semiquantitative score, inflammation by the rejection activity index, DSAs by Luminex.
A total of 134 PLBs from 94 patients were included. Fibrosis was detected in 87% (30% mild, 45% moderate, and 12% severe), 80% in the portal tracts. There was an increase in fibrosis between the 1-3 and the 4-6 y group (P = 0.01), then it was stable. Inflammation was observed in 44% (30% mild, 13% moderate, and 1% severe), 90% in the portal tracts. Anti-HLA II (IgG) DSAs were detected in 14 of 40 (35%). Portal fibrosis was associated with portal inflammation in the 1-3 y group (P = 0.04). Low immunosuppression levels were correlated with sinusoidal fibrosis (P = 0.04) and DSA positivity (P = 0.006). There was no statistically significant correlation between DSA positivity and the presence of graft fibrosis or inflammation.
This study corroborates the concept of an early evolution of silent graft fibrosis. Suboptimal immunosuppression may play a role in the development of fibrosis and DSAs.
移植肝纤维化和炎症对小儿肝移植自然病程的影响仍存在争议。我们的目的是评估在方案肝活检（PLB）时移植后纤维化和炎症随时间的演变、纤维化的危险因素、供者特异性抗体（DSA）的存在情况，以及/或者它们与移植肝和受者因素的相关性。
对至少进行过1次PLB的小儿肝移植受者进行了一项单中心、回顾性（2000 - 2019年）横断面研究，随后对至少进行过2次PLB的受者进行了纵向评估。通过移植肝纤维化半定量评分评估纤维化，通过排斥反应活动指数评估炎症，通过Luminex检测DSA。
共纳入了94例患者的134次PLB。87%检测到纤维化（30%为轻度，45%为中度，12%为重度），80%位于门静脉区。1 - 3岁组和4 - 6岁组之间纤维化有所增加（P = 0.01），然后保持稳定。44%观察到炎症（30%为轻度，13%为中度，1%为重度），90%位于门静脉区。40例中有14例（35%）检测到抗HLA II（IgG）DSA。1 - 3岁组门静脉纤维化与门静脉炎症相关（P = 0.04）。低免疫抑制水平与窦性纤维化（P = 0.04）和DSA阳性（P = 0.006）相关。DSA阳性与移植肝纤维化或炎症的存在之间无统计学显著相关性。
本研究证实了移植肝隐匿性纤维化早期演变的概念。免疫抑制不足可能在纤维化和DSA的发生中起作用。
