High hairy and enhancer of split 1 and low SOX17 immunohistochemical hepatic expression is associated with human biliary atresia

Abstract

Background Early discrimination of biliary atresia (BA) from other causes of neonatal cholestasis is a cornerstone for successful surgical intervention. To date, the exact etiology of BA remains elusive. We aimed to investigate the hepatic expression of hairy and enhancer of split 1 (HES1) and SOX17 in infants with BA compared with non-BA causes of cholestasis. Methods The study included 61 infants with cholestasis in two groups, BA (n=32) and non-BA (n=29). HES1 and SOX17 hepatic expression was evaluated in biliary epithelial cells as proportion×intensity for the total score. Results The frequency of positive HES1 expression was significantly higher in BA (84.8%) compared with non-BA (35.7%). In addition, the HES1 score was significantly higher in BA than in non-BA. The frequency of high intensity staining was significantly higher in BA (50%) compared with non-BA (20%). All patients were positive for SOX17. The SOX17 score was significantly lower in BA compared with non-BA. Furthermore, the occurrence of low-intensity staining was significantly higher in BA (84.4%) compared with non-BA (46.4%). Clay stool, higher gamma glutamyl transpeptidase, ductular proliferation, bile plugs, and portal edema are associated with positive HES1 and low SOX17 expression. Furthermore, abnormal gallbladder is associated with low SOX17 expression. Conclusion Positive HES1 and low SOX17 expression are associated significantly with BA. These results support the potential role of these molecules in the etiopathogenesis of BA.