Madadi-Sanjani Omid, Bohlen Gunnar, Wehrmann Fabian, Andruszkow Julia, Khelif Karim, von Wasielewski Reinhard, Bantel Heike, Petersen Claus
Department of Pediatric Surgery, Hannover Medical School, 30625 Hannover, Germany.
Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
J Clin Med. 2021 Jun 19;10(12):2718. doi: 10.3390/jcm10122718.
In biliary atresia (BA), apoptosis is part of the pathomechanism, which results in progressive liver fibrosis. There is increasing evidence suggesting that apoptotic liver injury can be non-invasively detected by measuring the caspase activity in the serum. The purpose of this study was to investigate whether serological detection of caspase activation mirrors apoptotic liver injury in the infective murine BA-model and represents a suitable biomarker for BA in humans. Analysis showed increased caspase-3 activity and apoptosis in the livers of cholestatic BALB/c mice, which correlated significantly with caspase activation in the serum. We then investigated caspase activation and apoptosis in liver tissues and sera from 26 BA patients, 23 age-matched healthy and 11 cholestatic newborns, due to other hepatopathies. Compared to healthy individuals, increased caspase activation in the liver samples of BA patients was present. Moreover, caspase-3 activity was significantly higher in sera from BA infants compared to patients with other cholestatic diseases (sensitivity 85%, specificity 91%). In conclusion, caspase activation and hepatocyte apoptosis play an important role in experimental and human BA. We demonstrated that serological detection of caspase activation represents a reliable non-invasive biomarker for monitoring disease activity in neonatal cholestatic liver diseases including BA.
在胆道闭锁（BA）中，细胞凋亡是发病机制的一部分，会导致进行性肝纤维化。越来越多的证据表明，通过测量血清中的半胱天冬酶活性可以非侵入性地检测凋亡性肝损伤。本研究的目的是调查血清学检测半胱天冬酶激活是否反映感染性小鼠BA模型中的凋亡性肝损伤，并代表人类BA的合适生物标志物。分析显示，胆汁淤积性BALB/c小鼠肝脏中的半胱天冬酶-3活性增加和细胞凋亡增加，这与血清中的半胱天冬酶激活显著相关。然后，我们调查了26例BA患者、23例年龄匹配的健康人和11例因其他肝病导致胆汁淤积的新生儿的肝组织和血清中的半胱天冬酶激活和细胞凋亡情况。与健康个体相比，BA患者肝脏样本中的半胱天冬酶激活增加。此外，与其他胆汁淤积性疾病患者相比，BA婴儿血清中的半胱天冬酶-3活性显著更高（敏感性85%，特异性91%）。总之，半胱天冬酶激活和肝细胞凋亡在实验性和人类BA中起重要作用。我们证明，血清学检测半胱天冬酶激活是监测包括BA在内的新生儿胆汁淤积性肝病疾病活动的可靠非侵入性生物标志物。
