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

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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.

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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.

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Authors and Affiliations

  1. Department of Pediatrics, Affiliated Hospital of Nan**g University of Chinese Medicine, Nan**g, China

    Wei-Wei Li, Qi-Gang Dai, Li-Li Lin, Tong **e, Jia-Lei Tao, **-Jun Shan & Shou-Chuan Wang

  2. Medical Metabolomics Center, Nan**g University of Chinese Medicine, Nan**g, China

    Wei-Wei Li, Li-Li Lin, Tong **e, Jia-Lei Tao & **-Jun Shan

  3. TCM Department, Bei**g Children’s Hospital Affiliated to Capital Medical University, Bei**g, China

    Yan Yang

  4. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nan**g University of Chinese Medicine, Nan**g, China

    Li-Li He

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  1. Wei-Wei Li
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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.

Corresponding authors

Correspondence to **-Jun Shan or Shou-Chuan Wang.

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Authors declare no conflict of interest.

Ethical approval

The study was approved by the ethics committee of Bei**g Children’s Hospital, Bei**g, 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.

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

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Li, WW., Yang, Y., Dai, QG. et al. Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome. Metabolomics 14, 90 (2018). https://doi.org/10.1007/s11306-018-1387-z

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  • DOI: https://doi.org/10.1007/s11306-018-1387-z

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