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Plasma amyloid-beta levels correlated with impaired hepatic functions: An adjuvant biomarker for the diagnosis of biliary atresia
oleh: Hongyu Lyu, Yongqin Ye, Yongqin Ye, Vincent Chi Hang Lui, Vincent Chi Hang Lui, Weifang Wu, Weifang Wu, Patrick Ho Yu Chung, Patrick Ho Yu Chung, Kenneth Kak Yuen Wong, Kenneth Kak Yuen Wong, Hung-Wing Li, Man Shing Wong, Paul Kwong Hang Tam, Bin Wang
Format: | Article |
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Diterbitkan: | Frontiers Media S.A. 2022-09-01 |
Deskripsi
BackgroundBiliary 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 (Aβ) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma Aβ levels correlate with hepatic dysfunctions and could be a biomarker for BA remains unknown.MethodPlasma samples of 11 BA and 24 controls were collected for liver function test, Aβ40 and Aβ42 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 Aβ42/Aβ40 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 Aβ42/Aβ40 for BA. Diagnostic enhancement was further evaluated by binary regression ROC analysis of Aβ42/Aβ40 combined with other hepatic function parameters.ResultsPlasma Aβ42/Aβ40 was elevated in BA patients. Aβ42 displayed a weak positive correlation with γ-glutamyl transpeptidase (GGT) (Pearson’s correlation = 0.349), while there was no correlation for Aβ40 with hepatic functions. Aβ42/Aβ40 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). Aβ42/Aβ40 showed an acceptable predictive power for cholestasis [AUC = 0.746 (95% CI: 0.552–0.941), p < 0.05]. Diagnostic powers of Aβ42/Aβ40 together with hepatic function parameters for cholestasis were markedly improved compared to any indicator alone. Neither Aβ42/Aβ40 nor hepatic function parameters displayed sufficient power in discriminating BA from choledochal cysts (CC); however, combinations of Aβ42/Aβ40 + 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.ConclusionAβ42/Aβ40 is a good indicator for cholestasis, but alone is insufficient for a distinction of BA from non-BA. However, Aβ42/Aβ40 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.