Increased Serum Levels of Activated Caspases in Murine and Human Biliary Atresia

Author:

Madadi-Sanjani OmidORCID,Bohlen Gunnar,Wehrmann Fabian,Andruszkow Julia,Khelif Karim,von Wasielewski Reinhard,Bantel Heike,Petersen Claus

Abstract

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.

Publisher

MDPI AG

Subject

General Medicine

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Progress in Biomarkers Related to Biliary Atresia;Journal of Clinical and Translational Hepatology;2024-01-30

2. Development of liver inflammatory injury in biliary atresia: from basic to clinical research;Pediatric Surgery International;2023-05-30

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