S Pandurangi et al. Hepatology 2024; 80: 152-162 Open Access!.Diagnostic accuracy of serum matrix metalloproteinase-7 as a biomarker of biliary atresia in a large North American cohort

Methods: MMP-7 was measured in serum samples of 399 infants (North America)18 with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays.

Key findings:

• On the single-plex assay, MMP-7 generated an AUROC of 0.90. At cutoff 52.8 ng/mL, it produced sensitivity = 94.03%, specificity = 77.78%, positive predictive value = 64.46%, and negative predictive value = 96.82% for BA.
• MMP-7 outperformed other parameters. AUROC for gamma-glutamyl transferase = 0.81 (CI: 0.77–0.86), stool color = 0.68 (CI: 0.63–0.73), and pathology = 0.84 (CI: 0.76–0.91).  Obstructive features on pathology were the second-best predictor of BA.
• GGT cutoff was 267.5 U/L (per personal communication with senior author) with sensitivity of 86.6%, and specificity of 77.4%
• Similar results were found with TR-FRET assay with cut-off of 18.2 ng/mL.
• 6% (False-negatives) of BA patients had MMP-7 levels below the cutoff
• 22% (False-positives) of non-BA patients had MMP-7 levels above the cutoff. This included 7 of 8 choledochal cyst patients, 8 of 17 with A1AT, and 13 of 98 with indeterminate cholestasis

In the discussion, the authors note that MMP-7 has performed better in studies with Asian populations, MMP-7 could be useful for dried blood spots in newborns, and could be useful as a measure of successful HPE; continued elevation of MMP-7 has been associated with hepatic fibrosis.

My take: This study shows that MMP-7 is not a perfect assay but often quite helpful. The exact cutoff depends on the specific assay that is utilized. Also, this study shows that checking for A1AT and checking an ultrasound to exclude choledochal cyst need to continue to be done early in the evaluation process.

Related blog posts:

• MMP-7 Helps Sort Out Biliary Atresia from Parenteral Nutrition-Associated Liver Disease
• More Data, More Nuance with MMP-7: Best Biliary Atresia Biomarker
• Don’t Put the Cart Before the Horse: Biliary Atresia Screening
• Why Didn’t Screening for Biliary Atresia Improve Outcome In This Study?
• Be Careful with Biliary Atresia Diagnostic Biomarkers
• Dried Blood Spot Testing for Biliary Atresia
• Landmark Study on Universal Screening for Biliary Atresia -It Works!
• Online Aspen Webinar (Part 5) -Biliary Atresia Diagnosis and Screening

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.