Protocol for a diagnostic accuracy study to develop diagnosis algorithm for biliary atresia using MMP-7 (DIABA-7 study): a study recruiting from Chinese Biliary Atresia Collaborative Network

Introduction Biliary atresia is a severe liver disease in neonates, and the prognosis partially depends on the age at which infants undergo the Kasai procedure. Matrix metalloproteinase-7 (MMP-7) was confirmed to have significant value in the diagnosis of biliary atresia. However, so far, the reference range and its cut-off value for diagnosing biliary atresia have not been established yet. Methods and analysis DIagnosis Algorithm for Biliary Atresia (DIABA-7) is a prospective diagnostic test. Cholestatic infants and normal controls within 150 days of age are recruiting from the Chinese Biliary Atresia Collaborative Network. The serum samples and dried blood spot (DBS) samples are obtained to detect MMP-7 concentrations using an ELISA kit. The reference standard is the intraoperative exploration and subsequent histological examination of liver biopsies. Lambda-Mu-Sigma (LMS) method is used to calculate the normal range of serum MMP-7 of each age group. Receiver operating characteristics (ROC) curves are constructed to calculate the best cut-off point and area under the curve for the index test. The sensitivity, specificity, positive predictive value and negative predictive value are used to show the diagnostic accuracy. Pearson correlation coefficient test is applied to assess the correlation of serum MMP-7 and DBS MMP-7. Ethics and dissemination This study was reviewed and approved by the Ethics Committee of Children’s Hospital of Fudan University (Number 2020–296). Dissemination will be guided by investigators and patients. The aim is to publish the study results in a high-quality peer-reviewed journal and present the findings at international academic meetings. Trial registration number ChiCTR2000032983.

[1]  Ruchi Bansal,et al.  Matrix Metalloproteinases as Potential Biomarkers and Therapeutic Targets in Liver Diseases , 2020, Cells.

[2]  Junfeng Wang,et al.  Serum MMP-7 in the Diagnosis of Biliary Atresia , 2019, Pediatrics.

[3]  Y. Jeng,et al.  Quantification of Serum Matrix Metallopeptide 7 Levels May Assist in the Diagnosis and Predict the Outcome for Patients with Biliary Atresia , 2019, The Journal of pediatrics.

[4]  G. Berg,et al.  Behavior of Metalloproteinases in Adipose Tissue, Liver and Arterial Wall: An Update of Extracellular Matrix Remodeling , 2019, Cells.

[5]  Guo-qing Cao,et al.  Diagnostic Accuracy of Serum Matrix Metalloproteinase‐7 for Biliary Atresia , 2018, Hepatology.

[6]  Gong Chen,et al.  Development and Validation of Novel Diagnostic Models for Biliary Atresia in a Large Cohort of Chinese Patients , 2018, EBioMedicine.

[7]  S. Bryan,et al.  Province-wide Biliary Atresia Home Screening Program in British Columbia: Evaluation of First 2 Years , 2018, Journal of pediatric gastroenterology and nutrition.

[8]  K. Bove,et al.  Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia , 2017, Science Translational Medicine.

[9]  M. Davenport,et al.  Long-term outlook in biliary atresia. , 2017, Seminars in pediatric surgery.

[10]  Gong Chen,et al.  Surgical outcome and etiologic heterogeneity of infants with biliary atresia who received Kasai operation less than 60 days after birth , 2017, Medicine.

[11]  C. Y. Ooi,et al.  Early and Peri-operative Prognostic Indicators in Infants Undergoing Hepatic Portoenterostomy for Biliary Atresia: a Review , 2017, Current Gastroenterology Reports.

[12]  Yan-Hong Gu,et al.  Modified stool color card with digital images was efficient and feasible for early detection of biliary atresia—a pilot study in Beijing, China , 2016, World Journal of Pediatrics.

[13]  Xiaolin Wang,et al.  Comparison of different noninvasive diagnostic methods for biliary atresia: a meta-analysis , 2016, World Journal of Pediatrics.

[14]  Amy G. Feldman,et al.  Biliary Atresia: Clinical Lessons Learned , 2015, Journal of pediatric gastroenterology and nutrition.

[15]  T. Ohkubo,et al.  Stool color card screening for early detection of biliary atresia and long-term native liver survival: a 19-year cohort study in Japan. , 2015, The Journal of pediatrics.

[16]  M. Davenport Biliary atresia: clinical aspects. , 2012, Seminars in pediatric surgery.

[17]  Mei-Hwei Chang,et al.  AUTOIMMUNE, CHOLESTATIC AND BILIARY DISEASE Universal Screening for Biliary Atresia Using an Infant Stool Color Card in Taiwan , 2008 .

[18]  Shan-Ming Chen,et al.  Screening for Biliary Atresia by Infant Stool Color Card in Taiwan , 2006, Pediatrics.

[19]  J. Levy,et al.  Biliary atresia. , 1985, Pediatric annals.

[20]  D. Alagille Extrahepatic Biliary Atresia , 1984, Hepatology.