Bile acid profiles in neonatal intrahepatic cholestasis caused by citrin deficiency

•We established an LC-MS/MS method to simultaneously quantify plasma bile acids•Bile acid profiles of infants with NICCD, non-NICCD and infant controls were examined•Plasma bile acid profile of NICCD patients was distinct from that of non-NICCD ones or infant controls•Combined ratios of plasma primary/secondary and conjugated/free bile acid may be useful for differential diagnosis of NICCD

BackgroundNeonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is characterized by conjugated hyperbilirubinemia and increased plasma bile acid concentrations. However, the underlying mechanisms remain unclear. We established a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneously quantifying plasma bile acids and examined bile acid profiles in NICCD infants.MethodsWe measured 15 bile acids within 15 min and found a wide linear range for individual bile acids.ResultsThe within-run and run-to-run CV of all bile acids was 1.2-10.9% and 3.1-10.8%, respectively, with a mean recovery of 90.5-112.6%. Compared to infants with citrullinemia without mutations in SLC25A13 (non-NICCD), NICCD infants showed increased plasma total bile acid concentrations (mean: 201 vs. 42 μM, p < 0.001), with a distinct bile acid profile characterized by increased conjugated primary bile acid concentrations. The calculated ratios, including primary/secondary bile acid (714 vs. 235, p < 0.05) and conjugated/free bile acid (371 vs. 125, p < 0.05) ratios, were higher in NICCD infants. The area under receiver operating characteristic curve for conjugated/free bile acid ratio to identify infants with NICCD was 0.871 (95% confidence interval, 0.713-1.0).ConclusionsTogether, our findings indicated plasma bile acid profile as a potential noninvasive diagnostic biomarker for NICCD.