Histopathological expression of Yes-associated protein in neonatal cholestasis

Abstract

Biliary atresia (BA) is a common cause of persistent neonatal cholestasis and liver transplantation in the pediatric population. Yes-associated protein (YAP) has also been shown to be necessary for development of bile ducts and adaptive responses within the gastrointestinal tract. We aimed to evaluate the YAP expression in liver tissues of infants with neonatal cholestasis as well as its diagnostic potential in the differential diagnosis of BA. This prospective study included 100 infants with neonatal cholestasis. After full history taking, thorough clinical examination, routine investigations, and histopathological assessment, the patients were allocated as BA and non-BA; fifty patients in each group. Ten liver biopsies from 10 donors of liver transplant recipients served as controls. Diagnosis of BA was confirmed by operative cholangiography. Hepatic expression of YAP was assessed by immunohistochemical staining. Presence of clay stool, elevated GGT and absence of gall bladder contractility were the main preliminary signs alarming for the possibility of BA. Bile ductular and interlobular biliary epithelium and hepatic lobule expression of YAP in patients with BA was significantly higher than that in Non-BA group (P<0.05). There was no or weak positive YAP expression in normal liver of transplant donors. Positive YAP immunohistochemical had a sensitivity of 80% and a specificity of 94% with accuracy 87% in discrimination between BA and non-BA group (P-value<0.0001). Hepatic expression of YAP was significantly higher in BA than in non-BA group and could discriminate BA from other causes of cholestasis.