Elevated bile acids in newborns with Biliary Atresia (BA)

Abstract

Biliary Atresia (BA), a result from inflammatory destruction of the intrahepatic and extrahepatic bile ducts, is a severe hepatobiliary disorder unique to infancy. Early diagnosis and Kasai operation greatly improve the outcome of BA patients, which encourages the development of early screening methods. Using HPLC coupled tandem mass spectrometry, we detected primary bile acids content in dried blood spots obtained from 8 BA infants, 17 neonatal jaundice and 292 comparison infants at 3-4 days of life. Taurocholate (TC) was significantly elevated in biliary atresia infants (0.98 ± 0.62 µmol/L) compared to neonatal jaundice (0.47 ± 0.30 µmol/L) and comparison infants (0.43 ± 0.40 µmol/L), with p=0.0231 and p=0.0016 respectively. The area under receiver operating characteristic (ROC) curve for TC to discriminate BA and comparison infants was 0.82 (95% confidence interval: 0.72-0.92). A cutoff of 0.63 µmol/L produced a sensitivity of 79.1% and specificity of 62.5%. The concentrations of total bile acids were also raised significantly in BA compared to comparison infants (6.62 ± 3.89 µmol/L vs 3.81 ± 3.06 µmol/L, p=0.0162), with the area under ROC curve of 0.75 (95% confidence interval: 0.61-0.89). No significant difference was found between the bile acids of neonatal jaundice and that of comparison infants. The early increase of bile acids indicates the presentation of BA in the immediate newborn period and the possibility of TC as newborn screening marker.

Figure 1. Boxplots of GC (A), GCDC (B), TC (C) and TCDC (D) in dried blood spots of biliary atresia (n = 8), neonatal jaundice (n = 17) and comparison infants (n = 292).

The concentrations of GC, GCDC, TC, and TCDC in BA were significantly higher than those of comparison infants (p<0.05). TC was also significantly elevated in BA compared to neonatal jaundice. No significant difference was observed between neonatal jaundice and comparison infants. BA: biliary atresia infants, Jaun: neonatal jaundice infants, NC: comparison infants.

Figure 2. Boxplot of total bile acids in dried blood spots of biliary atresia (n = 8), neonatal jaundice (n = 17) and comparison infants (n = 292).

The level of total bile acids in BA was raised significantly compared to comparison infants, with p = 0.0162. BA: biliary atresia infants, Jaun: neonatal jaundice infants, NC: comparison infants.

Figure 3. Receiver operating charactristic curves to discriminate BA and comparison infants for concentrations of TC and total bile acids.

The area under the curve was 0.82 (95% confidence interval: 0.72–0.92) for TC and 0.75 (95% confidence interval: 0.61–0.89) respectively, with p = 0.01976.