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Reduced Immunohistochemical Expression of Hnf1β and FoxA2 in Liver Tissue Can Discriminate Between Biliary Atresia and Other Causes of Neonatal Cholestasis

Shaalan, Usama F., PhD*; Ibrahim, Noha L., MSc*; Ehsan, Nermine A., MD, PhD; Sultan, Mervat M., MD; Naser, Ghada M., PhD*; Abd El-Fatah, Mohamed O., PhD

Applied Immunohistochemistry & Molecular Morphology: April 2019 - Volume 27 - Issue 4 - p e32–e38
doi: 10.1097/PAI.0000000000000638
Online Articles: Research Article

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.

*Molecular Diagnostics and Therapeutics Department

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Sadat City

Department of Pathology, National Liver Institute, Menoufia University, Menoufia, Egypt

The authors declare no conflict of interest.

Reprints: Nermine A. Ehsan, MD, PhD, Department of Pathology, National Liver Institute, Menoufia University, Menoufia, Gamal Abdel Nasser Street, Shebin El Kom 32511 Egypt (e-mail:

Received August 5, 2017

Accepted December 15, 2017

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