Shaalan Usama F, Ibrahim Noha L, Ehsan Nermine A, Sultan Mervat M, Naser Ghada M, Abd El-Fatah Mohamed O
Molecular Diagnostics and Therapeutics Department.
Department of Pathology, National Liver Institute, Menoufia University, Menoufia, Egypt.
Appl Immunohistochem Mol Morphol. 2019 Apr;27(4):e32-e38. doi: 10.1097/PAI.0000000000000638.
Biliary atresia (BA) is a necroinflammatory occlusive cholangiopathy that affects infants. Genetic and environmental factors has been proposed for its occurrence. The objectives of this study was to investigate the protein expression of 2 important genes regulating ductal plate remodeling, hepatocyte nuclear factor 1-beta (Hnf1β) and the fork head box protein A2 (FoxA2) in liver tissue from patients with BA and to compare their expression with other causes of neonatal cholestasis (NC). This retrospective study included 60 pediatric patients, 30 with BA and 30 with NC. Immunohistochemistry of Hnf1β and FoxA2 was performed on liver tissues from studied patients as well as 20 healthy subjects. Statistical analysis between immunohistochemistry results and other parameters was performed. Liver tissue from patients with BA revealed reduced Hnf1β and FoxA2 immunoexpression. A strong significant statistical difference between BA and NC group (P<0.0001) with regard to Hnf1β and FoxA2 immunoexpression was evident. Moreover, Hnf1β was significantly correlated with FoxA2 immunoexpression, stage of fibrosis, bile ductular proliferation, and bile plugs in bile ductules. Hnf1β immunoreaction in BA cases showed 76.7% sensitivity, 90% specificity, 88.5% positive predictive value, 79.4% negative predictive value, and 83.4% accuracy. FoxA2 expression in BA cases revealed 70.0% sensitivity, 80.0% specificity, 77.8% positive predictive value, 72.7% negative predictive value, 75.0% accuracy. Hnf1β and FoxA2 immunoexpression could differentiate between BA from other cause of NC.
胆道闭锁（BA）是一种影响婴儿的坏死性炎症性闭塞性胆管病。其发病机制涉及遗传和环境因素。本研究旨在调查调节胆管板重塑的两个重要基因，即肝细胞核因子1β（Hnf1β）和叉头框蛋白A2（FoxA2）在BA患者肝组织中的蛋白表达，并与其他新生儿胆汁淤积（NC）病因进行表达比较。这项回顾性研究纳入了60例儿科患者，其中30例为BA患者，30例为NC患者。对研究患者以及20名健康受试者的肝组织进行了Hnf1β和FoxA2的免疫组织化学检测。对免疫组织化学结果与其他参数进行了统计分析。BA患者的肝组织显示Hnf1β和FoxA2免疫表达降低。在Hnf1β和FoxA2免疫表达方面，BA组与NC组之间存在显著的统计学差异（P<0.0001）。此外，Hnf1β与FoxA2免疫表达、纤维化程度、胆管增生以及胆小管内胆汁栓显著相关。BA病例中Hnf1β免疫反应的敏感性为76.7%，特异性为90%，阳性预测值为88.5%，阴性预测值为79.4%，准确率为83.4%。BA病例中FoxA2表达的敏感性为70.0%，特异性为80.0%，阳性预测值为77.8%，阴性预测值为72.7%，准确率为75.0%。Hnf1β和FoxA2免疫表达可区分BA与其他NC病因。
