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Metabolomics

, 14:90 | Cite as

Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome

  • Wei-Wei Li
  • Yan Yang
  • Qi-Gang Dai
  • Li-Li Lin
  • Tong Xie
  • Li-Li He
  • Jia-Lei Tao
  • Jin-Jun ShanEmail author
  • Shou-Chuan WangEmail author
Original Article

Abstract

Introduction

Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring in the first 3 months of life. The most common causes of neonatal cholestasis are infantile hepatitis syndrome (IHS) and biliary atresia (BA). The clinical manifestations of the two diseases are too similar to distinguish them. However, early detection is very important in improving the clinical outcome of BA. Currently, a liver biopsy is the only proven and effective method used to differentially diagnose these two similar diseases in the clinic. However, this method is invasive. Therefore, sensitive and non-invasive biomarkers are needed to effectively differentiate between BA and IHS. We hypothesized that urinary metabolomics can produce unique metabolite profiles for BA and IHS.

Objectives

The aim of this study was to characterize urinary metabolomic profiles in infants with BA and IHS, and to identify differences among infants with BA, IHS, and normal controls (NC).

Methods

Urine samples along with patient characteristics were obtained from 25 BA, 38 IHS, and 38 NC infants. A non-targeted gas chromatography–mass spectrometry (GC–MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis (OPLS-DA) to explore the metabolomic profiles of BA, IHS, and NC infants.

Results

In total, 41 differentially expressed metabolites between BA vs. NC, IHS vs. NC, and BA vs. IHS were identified. N-acetyl-d-mannosamine and alpha-aminoadipic acid were found to be highly accurate at distinguishing between BA and IHS.

Conclusions

BA and IHS infants have specific urinary metabolomic profiles. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be used to discriminate BA from IHS.

Keywords

Biomarkers Metabolomics Biliary atresia Infantile hepatitis syndrome Urine 

Notes

Acknowledgements

This work is supported by Natural Science Foundation of China (81473725 and 81373688) and Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_1550). In addition, Wei-Wei Li especially wishes to thank Ji-Xuan He for his support over the past decade.

Author contributions

YY, SJJ and WSC designed the experiments. LWW and HLL involved in taking ethical clearance, collecting samples and managing their clinical details. LWW, DQG and TJL supervised GC–MS experiments. LWW, WSC, SJJ, XT and LLL contributed the reagents/materials/analysis tools, analysed the data and prepared the gures. LWW wrote the main manuscript. SJJ and WSC evaluated the manuscript critically and all the authors reviewed the manuscript.

Compliance with ethical standards

Conflict of interest

Authors declare no conflict of interest.

Ethical approval

The study was approved by the ethics committee of Beijing Children’s Hospital, Beijing, China. All protocols and procedures were adhered to institutional ethical standards and/or research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Prior informed consent was obtained from all the participants in the study with institutional review approval.

Supplementary material

11306_2018_1387_MOESM1_ESM.docx (17.2 mb)
Supplementary material 1 (DOCX 17582 KB)

References

  1. Abukawa, D., Ohura, T., Iinuma, K., & Tazawa, Y. (2001). An undescribed subset of neonatal intrahepatic cholestasis associated with multiple hyperaminoacidemia. Hepatology Research, 21, 8–13.CrossRefPubMedGoogle Scholar
  2. Al Mardini, H., Douglass, A., & Record, C. (2006). Amino acid challenge in patients with cirrhosis and control subjects: Ammonia, plasma amino acid and EEG changes. Metabolic Brain Disease, 21, 1–10.CrossRefPubMedGoogle Scholar
  3. Allen, M. B., & Walker, D. G. (1980). The isolation and preliminary characterization of N-acetyl-D-glucosamine kinase from rat kidney and liver. Biochemical Journal, 185, 565–575.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Assimakopoulos, S. F., Grintzalis, K., Thomopoulos, K. C., Papapostolou, I., Georgiou, C. D., Gogos, C., et al. (2008). Plasma superoxide radical in jaundiced patients and role of xanthine oxidase. The American Journal of the Medical Sciences, 336, 230–236.CrossRefPubMedGoogle Scholar
  5. Attallah, A. M., Toson el, S. A., El-Waseef, A. M., Abo-Seif, M. A., Omran, M. M., & Shiha, G. E. (2006). Discriminant function based on hyaluronic acid and its degrading enzymes and degradation products for differentiating cirrhotic from non-cirrhotic liver diseased patients in chronic HCV infection. Clinica Chimica Acta, 369, 66–72.CrossRefGoogle Scholar
  6. Balistreri, W. F., Grand, R., Hoofnagle, J. H., Suchy, F. J., Ryckman, F. C., Perlmutter, D. H., et al. (1996) Biliary atresia: Current concepts and research directions. Summary of a symposium. Hepatology 23, 1682–1692.CrossRefPubMedGoogle Scholar
  7. Bernabeu, A., Alfaro, A., Garcia, M., & Fernandez, E. (2009). Proton magnetic resonance spectroscopy (1H-MRS) reveals the presence of elevated myo-inositol in the occipital cortex of blind subjects. Neuroimage, 47, 1172–1176.CrossRefPubMedGoogle Scholar
  8. Bijl, E. J., Bharwani, K. D., Houwen, R. H., & de Man, R. A. (2013). The long-term outcome of the Kasai operation in patients with biliary atresia: A systematic review. The Netherlands Journal of Medicine, 71, 170–173.PubMedGoogle Scholar
  9. Blemings, K. P., Crenshaw, T. D., Swick, R. W., & Benevenga, N. J. (1994). Lysine-alpha-ketoglutarate reductase and saccharopine dehydrogenase are located only in the mitochondrial matrix in rat liver. Journal of Nutrition, 124, 1215–1221.CrossRefPubMedGoogle Scholar
  10. Bogdanos, D. P., Baum, H., Okamoto, M., Montalto, P., Sharma, U. C., Rigopoulou, E. I., et al. (2005). Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its Lactobacillus mimic. Hepatology, 42, 458–465.CrossRefPubMedGoogle Scholar
  11. Broadhurst, D., & Kell, D. (2006). Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics, 2, 171–196.CrossRefGoogle Scholar
  12. Cuzzolin, L., Mangiarotti, P., & Fanos, V. (2001). Urinary PGE(2) concentrations measured by a new EIA method in infants with urinary tract infections or renal malformations. Prostaglandins Leukot Essent Fatty Acids, 64, 317–322.CrossRefPubMedGoogle Scholar
  13. Davenport, M., Ong, E., Sharif, K., Alizai, N., McClean, P., Hadzic, N., et al. (2011). Biliary atresia in England and Wales: Results of centralization and new benchmark. Journal of Pediatric Surgery, 46, 1689–1694.CrossRefPubMedGoogle Scholar
  14. Dong, S., Zhan, Z. Y., Cao, H. Y., Wu, C., Bian, Y. Q., Li, J. Y., et al. (2017). Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease. World Journal of Gastroenterology, 23, 2771–2784.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Dunn, W. B., Broadhurst, D. I., Atherton, H. J., Goodacre, R., & Griffin, J. L. (2011). Systems level studies of mammalian metabolomes: The roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chemical Society Reviews, 40, 387–426.CrossRefPubMedGoogle Scholar
  16. Fanos, V., Antonucci, R., Barberini, L., & Atzori, L. (2012). Urinary metabolomics in newborns and infants. Advances in Clinical Chemistry, 58, 193–223.CrossRefPubMedGoogle Scholar
  17. Fiehn, O. (2001). Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks. Comparative and Functional Genomics, 2, 155–168.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Finelli, C., & Tarantino, G. (2017). Retraction: Nonalcoholic fatty liver disease, diet and gut microbiota. EXCLI Journal, 16, 1164.PubMedPubMedCentralGoogle Scholar
  19. Forton, D. M., Hamilton, G., Allsop, J. M., Grover, V. P., Wesnes, K., O’Sullivan, C., et al. (2008). Cerebral immune activation in chronic hepatitis C infection: A magnetic resonance spectroscopy study. Journal of Hepatology, 49, 316–322.CrossRefPubMedGoogle Scholar
  20. Fouquet, V., Alves, A., Branchereau, S., Grabar, S., Debray, D., Jacquemin, E., et al. (2005). Long-term outcome of pediatric liver transplantation for biliary atresia: A 10-year follow-up in a single center. Liver Transplantation, 11, 152–160.CrossRefPubMedGoogle Scholar
  21. Fujita, T., Hada, T., & Higashino, K. (1999). Origin of D- and L-pipecolic acid in human physiological fluids: A study of the catabolic mechanism to pipecolic acid using the lysine loading test. Clinica Chimica Acta, 287, 145–156.CrossRefGoogle Scholar
  22. Furukawa, K., Ohkawa, Y., Yamauchi, Y., Hamamura, K., Ohmi, Y., & Furukawa, K. (2012). Fine tuning of cell signals by glycosylation. Journal of Biochemistry, 151, 573–578.CrossRefPubMedGoogle Scholar
  23. Gou, X., Tao, Q., Feng, Q., Peng, J., Sun, S., Cao, H., et al. (2013). Urinary metabonomics characterization of liver fibrosis induced by CCl(4) in rats and intervention effects of Xia Yu Xue Decoction. Journal of Pharmaceutical and Biomedical Analysis, 74, 62–65.CrossRefPubMedGoogle Scholar
  24. Grover, V. P., Pavese, N., Koh, S. B., Wylezinska, M., Saxby, B. K., Gerhard, A., et al. (2012). Cerebral microglial activation in patients with hepatitis C: In vivo evidence of neuroinflammation. Journal of Viral Hepatitis, 19, e89-96.CrossRefPubMedGoogle Scholar
  25. Gu, H., Zhang, P., Zhu, J., & Raftery, D. (2015). Globally optimized targeted mass spectrometry: Reliable metabolomics analysis with broad coverage. Analytical Chemistry, 87, 12355–12362.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Gu, H. W., Carroll, P. A., Du, J. H., Zhu, J. J., Neto, F. C., Eisenman, R. N., et al. (2016). Quantitative method to investigate the balance between metabolism and proteome biomass: Starting from glycine. Angewandte Chemie-International Edition, 55, 15646–15650.CrossRefPubMedGoogle Scholar
  27. Guyot, C., & Stieger, B. (2011). Interaction of bile salts with rat canalicular membrane vesicles: Evidence for bile salt resistant microdomains. Journal of Hepatology, 55, 1368–1376.CrossRefPubMedGoogle Scholar
  28. Harms, E., Kreisel, W., Morris, H. P., & Reutter, W. (1973). Biosynthesis of N-acetylneuraminic acid in Morris hepatomas. European Journal of Biochemistry, 32, 254–262.CrossRefPubMedGoogle Scholar
  29. Hartley, J. L., Davenport, M., & Kelly, D. A. (2009). Biliary atresia. Lancet, 374, 1704–1713.CrossRefPubMedGoogle Scholar
  30. Higashino, K., Fujioka, M., & Yamamura, Y. (1971). The conversion of L-lysine to saccharopine and alpha-aminoadipate in mouse. Archives of Biochemistry and Biophysics, 142, 606–614.CrossRefPubMedGoogle Scholar
  31. Hinderlich, S., Stasche, R., Zeitler, R., & Reutter, W. (1997). A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Purification and characterization of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Journal of Biological Chemistry, 272, 24313–24318.CrossRefPubMedGoogle Scholar
  32. Holecek, M. (2017). Branched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation. Nutrition, 41, 80–85.CrossRefPubMedGoogle Scholar
  33. Hutzler, J., & Dancis, J. (1983). The determination of pipecolic acid: Method and results of hospital survey. Clinica Chimica Acta, 128, 75–82.CrossRefGoogle Scholar
  34. Kawasaki, H., Hori, T., Nakajima, M., & Takeshita, K. (1988). Plasma levels of pipecolic acid in patients with chronic liver disease. Hepatology, 8, 286–289.CrossRefPubMedGoogle Scholar
  35. Khanna, S., & Gopalan, S. (2007). Role of branched-chain amino acids in liver disease: The evidence for and against. Current Opinion in Clinical Nutrition and Metabolic Care, 10, 297–303.CrossRefPubMedGoogle Scholar
  36. Kikuchi, K., & Tsuiki, S. (1973). Purification and properties of UDP-N-acetylglucosamine 2′-epimerase from rat liver. Biochimica et Biophysica Acta, 327, 193–206.CrossRefPubMedGoogle Scholar
  37. Kind, T., Wohlgemuth, G., Lee, D. Y., Lu, Y., Palazoglu, M., Shahbaz, S., et al. (2009). FiehnLib: Mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography/mass spectrometry. Analytical Chemistry, 81, 10038–10048.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Kullak-Ublick, G. A., & Meier, P. J. (2000). Mechanisms of cholestasis. Clinical Liver Disease, 4, 357–385.CrossRefGoogle Scholar
  39. Lee, A., Chick, J. M., Kolarich, D., Haynes, P. A., Robertson, G. R., Tsoli, M., et al. (2011). Liver membrane proteome glycosylation changes in mice bearing an extra-hepatic tumor. Molecular & Cellular Proteomics, 10, M900538MCP200.CrossRefGoogle Scholar
  40. Lee, J. H., Seo, D. W., Lee, Y. S., Kim, S. T., Mun, C. W., Lim, T. H., et al. (1999). Proton magnetic resonance spectroscopy (1H-MRS) findings for the brain in patients with liver cirrhosis reflect the hepatic functional reserve. The American Journal of Gastroenterology, 94, 2206–2213.CrossRefPubMedGoogle Scholar
  41. Li, W. W., Shan, J. J., Lin, L. L., Xie, T., He, L. L., Yang, Y., et al. (2017). Disturbance in plasma metabolic profile in different types of human cytomegalovirus-induced liver injury in infants. Scientific Reports, 7, 15696.CrossRefPubMedPubMedCentralGoogle Scholar
  42. Majer, F., Trnka, L., Vitek, L., Jirkovska, M., Marecek, Z., & Smid, F. (2007). Estrogen-induced cholestasis results in a dramatic increase of b-series gangliosides in the rat liver. Biomedical Chromatography, 21, 446–450.CrossRefPubMedGoogle Scholar
  43. Mamas, M., Dunn, W. B., Neyses, L., & Goodacre, R. (2011). The role of metabolites and metabolomics in clinically applicable biomarkers of disease. Archives of Toxicology, 85, 5–17.CrossRefPubMedGoogle Scholar
  44. Marchesini, G., Bianchi, G., Merli, M., Amodio, P., Panella, C., Loguercio, C., et al. (2003). Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: A double-blind, randomized trial. Gastroenterology, 124, 1792–1801.CrossRefPubMedGoogle Scholar
  45. McKiernan, P. (2012). Neonatal jaundice. Clinics and Research in Hepatology and Gastroenterology, 36, 253–256.CrossRefPubMedGoogle Scholar
  46. McKiernan, P. J. (2002). Neonatal cholestasis. Seminars in Neonatology, 7, 153–165.CrossRefPubMedGoogle Scholar
  47. Memon, N., Weinberger, B. I., Hegyi, T., & Aleksunes, L. M. (2016). Inherited disorders of bilirubin clearance. Pediatric Research, 79, 378–386.CrossRefPubMedGoogle Scholar
  48. Muto, Y., Sato, S., Watanabe, A., Moriwaki, H., Suzuki, K., Kato, A., et al. (2006). Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis. Hepatology Research, 35, 204–214.PubMedGoogle Scholar
  49. Nicholson, J. K. (2006). Global systems biology, personalized medicine and molecular epidemiology. Molecular Systems Biology, 2, 52.CrossRefPubMedPubMedCentralGoogle Scholar
  50. O’Toole, A., Alakkari, A., Keegan, D., Doherty, G., Mulcahy, H., & O’Donoghue, D. (2012). Primary sclerosing cholangitis and disease distribution in inflammatory bowel disease. Clinical Gastroenterology and Hepatology, 10, 439–441.CrossRefPubMedGoogle Scholar
  51. Pascher, I., Lundmark, M., Nyholm, P. G., & Sundell, S. (1992). Crystal structures of membrane lipids. Biochimica et Biophysica Acta, 1113, 339–373.CrossRefPubMedGoogle Scholar
  52. Pena, I. A., Marques, L. A., Laranjeira, A. B., Yunes, J. A., Eberlin, M. N., MacKenzie, A., et al. (2017). Mouse lysine catabolism to aminoadipate occurs primarily through the saccharopine pathway; implications for pyridoxine dependent epilepsy (PDE). Biochimica et Biophysica Acta, 1863, 121–128.CrossRefPubMedGoogle Scholar
  53. Perez, M. J., & Briz, O. (2009). Bile-acid-induced cell injury and protection. World Journal of Gastroenterology, 15, 1677–1689.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Plitman, E., de la Fuente-Sandoval, C., Reyes-Madrigal, F., Chavez, S., Gomez-Cruz, G., Leon-Ortiz, P., et al. (2016). Elevated Myo-inositol, choline, and glutamate levels in the associative striatum of antipsychotic-naive patients with first-episode psychosis: A proton magnetic resonance spectroscopy study with implications for glial dysfunction. Schizophrenia Bulletin, 42, 415–424.CrossRefPubMedGoogle Scholar
  55. Rajendran, L., & Simons, K. (2005). Lipid rafts and membrane dynamics. Journal of Cell Science, 118, 1099–1102.CrossRefPubMedGoogle Scholar
  56. Roberts, E. A. (2003). Neonatal hepatitis syndrome. Seminars in Neonatology, 8, 357–374.CrossRefPubMedGoogle Scholar
  57. Rovira, A., Alonso, J., & Cordoba, J. (2008). MR imaging findings in hepatic encephalopathy. American Journal of Neuroradiology, 29, 1612–1621.CrossRefPubMedGoogle Scholar
  58. Russo, P., Magee, J., Anders, R., & Spino, C. (2016). Key histopathologic features of liver biopsies that distinguish biliary atresia from other causes of infantile cholestasis and their correlation with outcome: a multicenter study. American Journal of Surgical Pathology, 40, 1.CrossRefGoogle Scholar
  59. Sano, H., Nakazawa, T., Ando, T., Hayashi, K., Naitoh, I., Okumura, F., et al. (2011). Clinical characteristics of inflammatory bowel disease associated with primary sclerosing cholangitis. Journal of Hepato-Biliary-Pancreatic Sciences, 18, 154–161.CrossRefPubMedGoogle Scholar
  60. Sira, M. M., Taha, M., & Sira, A. M. (2014). Common misdiagnoses of biliary atresia. European Journal of Gastroenterology & Hepatology, 26, 1300–1305.CrossRefGoogle Scholar
  61. Smid, V., Petr, T., Vanova, K., Jasprova, J., Suk, J., Vitek, L., et al. (2016). Changes in liver ganglioside metabolism in obstructive cholestasis: The role of oxidative stress. Folia Biologica, 62, 148–159.PubMedGoogle Scholar
  62. Sokol, R. J., Mack, C., Narkewicz, M. R., & Karrer, F. M. (2003). Pathogenesis and outcome of biliary atresia: Current concepts. Journal of Pediatric Gastroenterology and Nutrition, 37, 4–21.CrossRefPubMedGoogle Scholar
  63. Stirpe, F., Ravaioli, M., Battelli, M. G., Musiani, S., & Grazi, G. L. (2002). Xanthine oxidoreductase activity in human liver disease. The American Journal of Gastroenterology, 97, 2079–2085.CrossRefPubMedGoogle Scholar
  64. Struys, E. A., & Jakobs, C. (2010). Metabolism of lysine in alpha-aminoadipic semialdehyde dehydrogenase-deficient fibroblasts: Evidence for an alternative pathway of pipecolic acid formation. FEBS Letters, 584, 181–186.CrossRefPubMedGoogle Scholar
  65. Tam, P. K. H., Chung, P. H. Y., St Peter, S. D., Gayer, C. P., Ford, H. R., Tam, G. C. H., et al. (2017). Advances in paediatric gastroenterology. Lancet, 390, 1072–1082.CrossRefPubMedGoogle Scholar
  66. Tietge, U. J., Bahr, M. J., Manns, M. P., & Boker, K. H. (2003). Hepatic amino-acid metabolism in liver cirrhosis and in the long-term course after liver transplantation. Transplant International, 16, 1–8.CrossRefPubMedGoogle Scholar
  67. Tsugawa, H., Cajka, T., Kind, T., Ma, Y., Higgins, B., Ikeda, K., et al. (2015). MS-DIAL: Data-independent MS/MS deconvolution for comprehensive metabolome analysis. Nature Methods, 12, 523–526.CrossRefPubMedPubMedCentralGoogle Scholar
  68. van den Berg, R. A., Hoefsloot, H. C., Westerhuis, J. A., Smilde, A. K., & van der Werf, M. J. (2006). Centering, scaling, and transformations: Improving the biological information content of metabolomics data. BMC Genomics, 7, 142.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Verkade, H. J., Bezerra, J. A., Davenport, M., Schreiber, R. A., Mieli-Vergani, G., Hulscher, J. B., et al. (2016). Biliary atresia and other cholestatic childhood diseases: Advances and future challenges. Journal of Hepatology, 65, 631–642.CrossRefPubMedGoogle Scholar
  70. Vinayavekhin, N., Homan, E. A., & Saghatelian, A. (2010). Exploring disease through metabolomics. ACS Chemical Biology, 5, 91–103.CrossRefPubMedGoogle Scholar
  71. Wang, X., Lv, H., Zhang, G., Sun, W., Zhou, D., Jiao, G., et al. (2008). Development and validation of a ultra performance LC-ESI/MS method for analysis of metabolic phenotypes of healthy men in day and night urine samples. Journal of Separation Science, 31, 2994–3001.CrossRefPubMedGoogle Scholar
  72. Wang, X., Zhang, A., Han, Y., Wang, P., Sun, H., Song, G., et al. (2012). Urine metabolomics analysis for biomarker discovery and detection of jaundice syndrome in patients with liver disease. Molecular & Cellular Proteomics, 11, 370–380.CrossRefGoogle Scholar
  73. Weber-Mzell, D., Zaupa, P., Petnehazy, T., Kobayashi, H., Schimpl, G., Feierl, G., et al. (2006). The role of nuclear factor-kappa B in bacterial translocation in cholestatic rats. Pediatric Surgery International, 22, 43–49.CrossRefPubMedGoogle Scholar
  74. Xia, J., Broadhurst, D. I., Wilson, M., & Wishart, D. S. (2013). Translational biomarker discovery in clinical metabolomics: An introductory tutorial. Metabolomics, 9, 280–299.CrossRefPubMedGoogle Scholar
  75. Xia, J., Psychogios, N., Young, N., & Wishart, D. S. (2009). MetaboAnalyst: A web server for metabolomic data analysis and interpretation. Nucleic Acids Res, 37, W652-60.CrossRefPubMedGoogle Scholar
  76. Yang, J., Xu, G., Zheng, Y., Kong, H., Pang, T., Lv, S., et al. (2004). Diagnosis of liver cancer using HPLC-based metabonomics avoiding false-positive result from hepatitis and hepatocirrhosis diseases. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 813, 59–65.CrossRefPubMedGoogle Scholar
  77. Yang, J., Xu, G., Zheng, Y., Kong, H., Wang, C., Zhao, X., et al. (2005). Strategy for metabonomics research based on high-performance liquid chromatography and liquid chromatography coupled with tandem mass spectrometry. Journal of Chromatography A, 1084, 214–221.CrossRefPubMedGoogle Scholar
  78. Yao, W., Gu, H., Zhu, J., Barding, G., Cheng, H., Bao, B., et al. (2014). Integrated plasma and urine metabolomics coupled with HPLC/QTOF-MS and chemometric analysis on potential biomarkers in liver injury and hepatoprotective effects of Er-Zhi-Wan. Analytical and Bioanalytical Chemistry, 406, 7367–7378.CrossRefPubMedGoogle Scholar
  79. Ye, Q., Yin, W., Zhang, L., Xiao, H., Qi, Y., Liu, S., et al. (2017). The value of grip test, lysophosphatidlycholines, glycerophosphocholine, ornithine, glucuronic acid decrement in assessment of nutritional and metabolic characteristics in hepatitis B cirrhosis. PLoS ONE, 12, e0175165.CrossRefPubMedPubMedCentralGoogle Scholar
  80. Yu, J., Marsh, S., Hu, J., Feng, W., & Wu, C. (2016) The pathogenesis of nonalcoholic fatty liver disease: Interplay between diet, gut microbiota, and genetic background. Gastroenterology Research and Practice 2016, 2862173.PubMedPubMedCentralGoogle Scholar
  81. Zerbini, M. C., Gallucci, S. D., Maezono, R., Ueno, C. M., Porta, G., Maksoud, J. G., et al. (1997). Liver biopsy in neonatal cholestasis: A review on statistical grounds. Modern Pathology, 10, 793–799.PubMedGoogle Scholar
  82. Zhao, D., Han, L., He, Z., Zhang, J., & Zhang, Y. (2014). Identification of the plasma metabolomics as early diagnostic markers between biliary atresia and neonatal hepatitis syndrome. PLoS ONE, 9, e85694.CrossRefPubMedPubMedCentralGoogle Scholar
  83. Zhou, K., Wang, J., Xie, G., Zhou, Y., Yan, W., Pan, W., et al. (2015a). Distinct plasma bile acid profiles of biliary atresia and neonatal hepatitis syndrome. Journal of Proteome Research, 14, 4844–4850.CrossRefPubMedGoogle Scholar
  84. Zhou, K., Xie, G., Wang, J., Zhao, A., Liu, J., Su, M., et al. (2015b). Metabonomics reveals metabolite changes in biliary atresia infants. Journal of Proteome Research, 14, 2569–2574.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Wei-Wei Li
    • 1
    • 2
  • Yan Yang
    • 3
  • Qi-Gang Dai
    • 1
  • Li-Li Lin
    • 1
    • 2
  • Tong Xie
    • 1
    • 2
  • Li-Li He
    • 4
  • Jia-Lei Tao
    • 1
    • 2
  • Jin-Jun Shan
    • 1
    • 2
    Email author
  • Shou-Chuan Wang
    • 1
    Email author
  1. 1.Department of PediatricsAffiliated Hospital of Nanjing University of Chinese MedicineNanjingChina
  2. 2.Medical Metabolomics CenterNanjing University of Chinese MedicineNanjingChina
  3. 3.TCM DepartmentBeijing Children’s Hospital Affiliated to Capital Medical UniversityBeijingChina
  4. 4.Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina

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