Plasma amyloid-beta levels correlated with impaired hepatic functions: An adjuvant biomarker for the diagnosis of biliary atresia

Background: Biliary atresia (BA) is an infantile fibro-obstructive cholestatic disease with poor prognosis. An early diagnosis and timely Kasai portoenterostomy (KPE) improve clinical outcomes. Aggregation of amyloid-beta (A beta) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma A beta levels correlate with hepatic dysfunctions and could be a biomarker for BA remains unknown.Method: Plasma samples of 11 BA and 24 controls were collected for liver function test, A beta 40 and A beta 42 measurement by enzyme-linked immunosorbent assay (ELISA). Pearson's chi-squared test or Mann-Whitney U test was performed to assess differences between groups. Correlation between A beta 42/A beta 40 and liver function parameters was performed using Pearson analysis. The area under the receiver-operative characteristic (ROC) curve (area under curve; AUC) was measured to evaluate the diagnostic power of A beta 42/A beta 40 for BA. Diagnostic enhancement was further evaluated by binary regression ROC analysis of A beta 42/A beta 40 combined with other hepatic function parameters.Results: Plasma A beta 42/A beta 40 was elevated in BA patients. A beta 42 displayed a weak positive correlation with gamma-glutamyl transpeptidase (GGT) (Pearson's correlation = 0.349), while there was no correlation for A beta 40 with hepatic functions. A beta 42/A beta 40 was moderately correlated with GGT, total bile acid (TBA), direct bilirubin (DBIL) (Pearson's correlation = 0.533, 0.475, 0.480), and weakly correlated with total bilirubin (TBIL) (Pearson's correlation = 0.337). A beta 42/A beta 40 showed an acceptable predictive power for cholestasis [AUC = 0.746 (95% CI: 0.552-0.941), p < 0.05]. Diagnostic powers of A beta 42/A beta 40 together with hepatic function parameters for cholestasis were markedly improved compared to any indicator alone. Neither A beta 42/A beta 40 nor hepatic function parameters displayed sufficient power in discriminating BA from choledochal cysts (CC); however, combinations of A beta 42/A beta 40 + GGT along with any other hepatic function parameters could differentiate BA from CC-cholestasis (AUC = 1.000, p < 0.05) with a cut-off value as 0.02371, -0.28387, -0.34583, 0.06224, 0.01040, 0.06808, and 0.05898, respectively.Conclusion: A beta 42/A beta 40 is a good indicator for cholestasis, but alone is insufficient for a distinction of BA from non-BA. However, A beta 42/A beta 40 combined with GGT and one other hepatic function parameter displayed a high predictive power as a screening test for jaundiced neonates who are more likely to be BA, enabling them to early intraoperative cholangiography for BA confirmation and KPE to improve surgical outcomes. However, a multi-centers validation is needed before introduction into daily clinical practice.

Automated summary

Elevated plasma levels of A beta 42/A beta 40 were found in patients with biliary atresia (BA), showing correlations with liver function parameters and good predictive power for cholestasis. Combining A beta 42/A beta 40 with other hepatic function parameters significantly improved the diagnostic ability for BA, making it a potentially useful screening tool for jaundiced neonates.