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Dynamic analysis of serum MMP-7 and its relationship with disease progression in biliary atresia: a multicenter prospective study

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Abstract

Purpose

We aimed to assess the dynamic changing trend of serum matrix metalloproteinase-7 (MMP-7) in biliary atresia (BA) patients from diagnosis to LTx to further elucidate its clinical value in diagnosis and prognoses and its relationship with disease progression.

Methods

In this multicentre prospective study, 440 cholestasis patients (direct bilirubin level of > 17 μmol/L) were enrolled. Serum MMP-7 levels were measured using an enzyme-linked immunosorbent assay at diagnosis, 1 week, 2 weeks, 1 month, 6 weeks, 2 months, 3 months, 6 months and then every 6 months post-KPE. The medical record at each follow-up visit for post-Kasai portoenterostomy patient was collected and analyzed.

Results

Using a cut-off value of > 26.73 ng/mL, serum MMP-7 had an AUC of 0.954 in BA neonates and 0.983 in BA infants. A genetic mutation (G137D) was associated with low MMP-7 levels in serum of BA patients. MMP-7 showed a mediation effect on the association between inflammation and liver fibrosis in BA patients. Four dynamic patterns of serum MMP-7 post-KPE were associated with prognosis. Serum MMP-7 was the only significant predictor at 6 weeks post-KPE and the most accurate predictor at 3 months post-KPE of survival with the native liver in 2 years.

Conclusion

As one of the critical factors associated with BA occurrence and progression, serum MMP-7 can be used for early diagnosis of BA and post-KPE MMP-7 level is the earliest prognostic biomarker so far.

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Availability of data and material

The data can be obtained by reasonable request from the corresponding author. STT has access to all data.

Code availability

Not applicable.

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Funding

National Natural Science Foundations of China (Grant nos. 81670511 and 81270481).

Author information

Author notes

  1. Shuiqing Chi, Peipei Xu and Pu Yu contributed equally to this study.

Authors and Affiliations

  1. Department of Paediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Shuiqing Chi, Peipei Xu, Shuai Li, Yun Zhou, Xiangyang Li, Ying Zhou, Xi Zhang & Shaotao Tang

  2. Department of Neonatal Surgery, Xi’an Children’s Hospital, Xi’an, China

    Pu Yu & Guoqing Cao

  3. Department of Paediatric Surgery, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Haibin Wang

  4. Department of General Surgery, Shenzhen Children’s Hospital General Surgery Ward, Shenzhen, China

    Yongqin Ye

  5. Department of Paediatric General Surgery, Hebei Children’s Hospital of Hebei Medical University, Hebei, China

    Huizhong Niu

  6. Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Lei Xu & Pengcheng Cai

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  1. Shuiqing Chi
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Contributions

All authors contributed to the study conception and design. SQC and PPX collected, analyzed the data, and drafted the manuscript; PY collected the data and provided analytical oversight; PPX, SQC, PY and STT designed and supervised the study; HBW, YQY, GQC, SL, YZ, XZ, XYL, HZN, LX and PCC revised the manuscript for important intellectual content; GQC and SL offered technical or material support; STT provided administrative support; all authors read and approved the final manuscript.

Corresponding author

Correspondence to Shaotao Tang.

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Conflict of interest

Shuiqing Chi, Peipei Xu, Pu Yu, Guoqing Cao, Haibin Wang, Yongqin Ye, Shuai Li, Yun Zhou, Xiangyang Li, Ying Zhou, Xi Zhang, Huizhong Niu, Lei Xu, Pengcheng Cai, Shaotao Tang declare no competing interests.

Ethics approval

The research program was approved by the Institutional Review Board of each center, and this clinical trial was approved and registered in the Chinese clinical trial registry.

Consent to participate

Informed and written consent to participate in the study was obtained from all patients’ parents.

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All authors agreed to publish this manuscript.

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Supplementary Information

Below is the link to the electronic supplementary material.

12072_2022_10322_MOESM1_ESM.eps

Supplementary file1 Supplementary Fig. 1 (a) ROC curve of MMP-7 for the diagnosis of biliary atresia in neonates (b) ROC curve of MMP-7 for the diagnosis of biliary atresia (EPS 1031 KB)

12072_2022_10322_MOESM2_ESM.eps

Supplementary file2 Supplementary Fig. 2 The mediation analyses model to examine the mediation effect of MMP-7 on the relationship between liver inflammation grades and liver fibrosis classifications in BA patients (EPS 649 KB)

12072_2022_10322_MOESM3_ESM.eps

Supplementary file3 Supplementary Fig. 3 Dynamic MMP-7 patterns. (a) pattern 1 (b) pattern 2 (c) pattern 3 (d) pattern 4 (EPS 1863 KB)

Supplementary file4 (DOCX 15 KB)

Supplementary file5 (DOCX 18 KB)

Supplementary file6 (DOCX 14 KB)

Supplementary file7 (DOCX 14 KB)

Supplementary file8 (DOCX 14 KB)

Supplementary file9 (DOCX 14 KB)

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Chi, S., Xu, P., Yu, P. et al. Dynamic analysis of serum MMP-7 and its relationship with disease progression in biliary atresia: a multicenter prospective study. Hepatol Int 16, 954–963 (2022). https://doi.org/10.1007/s12072-022-10322-x

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  • DOI: https://doi.org/10.1007/s12072-022-10322-x

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