Can Neonatal Hepatitis Be More Fatal than Biliary Atresia?

Dınız, Gülden; Yıldırım, Hülya Tosun; Çalkavur, Şebnem; Ecevıt, Çiğdem; Olukman, Özgür; Tunçel, Tuba; Aktaş, Safiye

doi:10.3109/15513815.2014.999393

Cited by 2 publications

(3 citation statements)

References 15 publications

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“…Although etiology of BA is unclear, immune dysregulation plays important roles in pathogenesis of the disease . BA will eventually progress to liver cirrhosis , and the significantly higher expression of γ-glutamyltransferase levels possibly indicates worse hepatic damage in the BA group. The difference in amino acid metabolism may reflect the different causes of liver damages between BA and NHS. , …”

Section: Discussionmentioning

confidence: 99%

Metabonomics Reveals Metabolite Changes in Biliary Atresia Infants

et al. 2015

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Biliary atresia (BA) is a rare neonatal cholestatic disorder caused by obstruction of extra and intra hepatic bile ducts. If untreated, progressive liver cirrhosis will lead to death within two years. Early diagnosis and operation improve the outcome significantly. Infants with neonatal hepatitis syndrome (NHS) present similar symptoms, confounding the early diagnosis of BA. The lack of non-invasive diagnostic methods to differentiate BA from NHS greatly delays the surgery of BA infants, thus deteriorating the outcome. Here, we performed a metabolomics study in plasma of BA, NHS, and healthy infants using gas chromatography-time-of-flight mass spectrometry. Scores plots of orthogonal partial least square discriminant analysis clearly separated BA from NHS and healthy infants. Eighteen metabolites were found to be differentially expressed between BA and NHS, among which seven (L-glutamic acid, L-ornithine, L-isoleucine, L-lysine, L-valine, L-tryptophan, and L-serine) were amino acids. The altered amino acids were quantitatively verified using ultra-performance liquid chromatography-tandem mass spectrometry. Ingenuity pathway analysis revealed the network of “Cellular Function and Maintenance, Hepatic System Development and Function, Neurological Disease” was altered most significantly. This study suggests that plasma metabolic profiling has great potential in differentiating BA from NHS, and amino acid metabolism is significantly different between the two diseases.

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Section: Discussionmentioning

confidence: 99%

Metabonomics Reveals Metabolite Changes in Biliary Atresia Infants

et al. 2015

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“…Neonatal hepatitis syndrome (NHS) is another common cause of cholestasis in infants, confounding the diagnosis of BA. Most infants with NHS will usually return to normal at one year of age, while some are fatal …”

Section: Introductionmentioning

confidence: 99%

“…Most infants with NHS will usually return to normal at one year of age, 6 while some are fatal. 7 Bile acids are important regulatory molecules derived from cholesterol in the liver. Given the fact that hepatocytes synthesize primary bile acids and maintain a consistent size of bile acid pool systemically, 8 dysregulated bile acid synthesis and metabolism are often indicative of liver dysfunction.…”

Section: ■ Introductionmentioning

confidence: 99%

Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome

et al. 2015

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Biliary atresia (BA) is a severe chronic cholestasis disorder of infants that leads to death if not treated on time. Neonatal hepatitis syndrome (NHS) is another leading cause of neonatal cholestasis confounding the diagnosis of BA. Recent studies indicate that altered bile acid metabolism is closely associated with liver injury and cholestasis. In this study, we systematically measured the bile acid metabolome in plasma of BA, NHS, and healthy controls. Liver bile acids were also measured using biopsy samples from 48 BA and 16 NHS infants undergoing operative cholangiography as well as 5 normal adjacent nontumor liver tissues taken from hepatoblastoma patients as controls. Both BA and NHS samples had significantly elevated bile acid levels in plasma compared to normal controls. BA patients showed a distinct bile acid profile characterized by the higher taurochenodeoxycholic acid (TCDCA) level and lower chenodeoxycholic acid (CDCA) level than those in NHS patients. The ratio of TCDCA to CDCA in plasma was significantly higher in BA compared to healthy infants (p < 0.001) or NHS (p < 0.001). The area under receiver operating characteristic curve for TCDCA/CDCA to differentiate BA from NHS was 0.923 (95% CI: 0.862-0.984). These findings were supported by significantly altered expression levels of bile acid transporters and nuclear receptors in liver including farnesoid X receptor (FXR), small heterodimer partner (SHP), bile salt export pump (BSEP), and multidrug resistant protein 3 (MDR3) in BA compared to NHS. Taken together, the plasma bile acid profiles are distinct in BA, NHS, and normal infants, as characterized by the ratio of TCDCA/CDCA differentially distributed among the three groups of infants.

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Can Neonatal Hepatitis Be More Fatal than Biliary Atresia?

Cited by 2 publications

References 15 publications

Metabonomics Reveals Metabolite Changes in Biliary Atresia Infants

Metabonomics Reveals Metabolite Changes in Biliary Atresia Infants

Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome

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