Does amyloid β precursor protein gene expression have a role in diagnosis of biliary atresia?

Biliary atresia (BA) is an important cause of surgical jaundice. Although the precise etiology is unknown, β-amyloid (Aβ) has been observed around the bile ducts in BA livers. It is unclear whether Aβ plays a role in the pathogenesis of this disease. This study aims to assess the amyloid β precursor protein (APP) gene expression in infants with BA in comparison with other causes of neonatal cholestasis. This could help explore the role of Aβ in the pathogenesis and diagnosis of BA.

A prospective study was conducted at the outpatient clinic of Paediatric Hepatology, Gastroenterology, and Nutrition Department, National Liver Institute, Menoufia University, Shebin El Kom, Menoufia, Egypt during the period March 2022 to December 2022. Clinical data were gathered and laboratory and radiological investigations were conducted including β precursor protein gene expression measured in liver biopsies of the three groups using quantitative real-time PCR (qPCR).

Gene expression of APP was considerably higher in the BA group (p = 0.0001) compared to neonatal cholestasis (NC) patients. Gamma glutamyl transferase (GGT) and APP had a positive correlation (p = 0.001). No significant association was found between APP and fibrosis. APP was noticeably higher in BA than NC other than BA. Also, APP in BA was higher (statistically significant, p = 0.0001) than the control. There was no statistically significant difference among NC, BA, and control groups regarding APP (p = 0.07). Both males and females did not show significant differences as regards APP (p = 0.851). Age did not have a statistically significant correlation with APP (p = 0.532). Also, there were no correlations between APP and alkaline phosphatase (ALP), aspartate transaminase (AST), or total bilirubin (TB) (p > 0.05).

We concluded that the development and identification of BA may depend on the liver expression of serum APP. Surgeons may be able to carry out early intraoperative cholangiography for BA confirmation if the combination of APP with GGT and other hepatic function parameters exhibits a high predictive potential as a diagnostic test for BA. To evaluate this hypothesis, more research with sizable sample numbers is necessary.