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Diagnostic values of plasma matrix metalloproteinase-7, interleukin-8, and gamma-glutamyl transferase in biliary atresia

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Abstract

Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and liver fibrosis. The early diagnosis of BA is still challenging. This study aimed to evaluate the diagnostic values of matrix metalloprotease-7 (MMP-7), interleukin-8 (IL-8), and gamma-glutamyl transferase (GGT) in BA. Infants diagnosed with BA and non-BA between 2013 and 2018 were retrospectively analyzed. Plasma levels of MMP-7, IL-8, and GGT were measured in these infants. The receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were used to assess the diagnostic values of MMP-7, IL-8, and GGT. The expression of MMP-7 and IL-8 in the livers was detected by immunofluorescence staining. A total of 229 infants were enrolled in this study: 156 BA infants and 73 non-BA infants including 16 ones with infantile hepatitis syndrome. The plasma levels of MMP-7, IL-8, and GGT in BA infants had a median of 11.8 ng/mL (interquartile range, IQR: 5.3–57.5), 1.5 ng/mL (IQR: 1.0–2.8), and 381.0 U/L (IQR: 197.0–749.0), respectively, which were higher than non-BA subjects [MMP-7, 4.4 ng/mL (IQR: 3.3–6.1); IL-8, 0.7 ng/mL (IQR: 0.5–1.0); GGT, 59.0 U/L (IQR: 26.0–124.0)]. The AUC values of MMP-7, IL-8, and GGT for the diagnosis of BA were 0.8035, 0.8083, and 0.9126, respectively. The AUC values of MMP-7 + IL-8, MMP-7 + GGT, IL-8 + GGT, and MMP-7 + IL-8 + GGT for the diagnosis of BA were 0.8248, 0.9382, 0.9168, and 0.9392, respectively. The AUC values of MMP-7, IL-8, and GGT for differentiating BA infants with cholic stool from non-BA infants with cholic stool were 0.8006, 0.8258, and 0.9141, respectively. The expression of MMP-7 and IL-8 was increased in the cholangiocytes in BA livers.

   Conclusion: Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA and may be reliable biomarkers for BA.

What is Known:

• Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and progressive liver fibrosis.

• Although early diagnosis of BA is crucial for good outcomes, it remains a clinical challenge.

What is New:

• Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA.

• Plasma MMP-7, IL-8, and GGT have good accuracy for differentiating BA infants with cholic stool from non-BA infants with cholic stool.

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Upon reasonable request to the corresponding author.

Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AUC:

Area under the curve

BA:

Biliary atresia

CK19:

Cytokeratin 19

DBil:

Direct bilirubin

ELISA:

Enzyme-linked immunosorbent assay

GGT:

Gamma-glutamyl transferase

HPE:

Hepatic portoenterostomy

IHC:

Intrahepatic cholestasis

IHS:

Infantile hepatitis syndrome

IL-8:

Interleukin-8

IQR:

Interquartile range

MMP-7:

Matrix metalloprotease-7

ROC:

Receiver operating characteristic

TBA:

Total bile acid

TBil:

Total bilirubin

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Acknowledgements

The authors are grateful to Beilin Gu for helping in managing the samples and grateful to the funding support (the National Natural Science Foundation of China, 81974058).

Funding

This study was supported by the National Natural Science Foundation of China (81974058).

Author information

Author notes

  1. Bo Wu and Ying Zhou contributed equally to this work.

Authors and Affiliations

  1. Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China

    Bo Wu, Xinbei Tian, Wei Cai & Yongtao Xiao

  2. Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China

    Ying Zhou, Wei Cai & Yongtao Xiao

  3. Shanghai Institute of Pediatric Research, Shanghai, China

    Wei Cai & Yongtao Xiao

  4. Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China

    Wei Cai & Yongtao Xiao

Authors
  1. Bo Wu
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Contributions

Bo Wu, Ying Zhou, Wei Cai, and Yongtao Xiao designed the study, analyzed the data, and drafted the manuscript. Bo Wu, Ying Zhou, and Xinbei Tian performed the experiments. Wei Cai and Yongtao Xiao revised the manuscript. All authors have read and approved to submit the manuscript.

Corresponding authors

Correspondence to Wei Cai or Yongtao Xiao.

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Ethics approval

The study was approved by the Faculty of Medicine’s Ethics Committee of Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (XHEC-D-2022–117).

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Informed consent was obtained from all individual participants’ guardians included in the study.

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All authors gave their consent for publication.

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The authors declare no competing interests.

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Communicated by Peter de Winter

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Wu, B., Zhou, Y., Tian, X. et al. Diagnostic values of plasma matrix metalloproteinase-7, interleukin-8, and gamma-glutamyl transferase in biliary atresia. Eur J Pediatr 181, 3945–3953 (2022). https://doi.org/10.1007/s00431-022-04612-7

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