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. 2022 Mar-Apr;27(2):227-235.
doi: 10.4103/jiaps.JIAPS_389_20. Epub 2022 Mar 1.

Serum Matrix Metalloproteinase 7 as a Diagnostic and Prognostic Biomarker for Extrahepatic Biliary Atresia

Teg Rabab Singh  1 , Prabudh Goel  1 , Minu Bajpai  1 , Devasenathipathy Kandasamy  2 , Rohan Malik  3 , Rajni Yadav  4 , Shyam Prakash  5 , Kalaivani Mani  6 , Madhavi Tripathi  7 , Devendra Kumar Yadav  1 , Anjan Kumar Dhua  1 , Vishesh Jain  1 , Sandeep Agarwala  1
Affiliations

Serum Matrix Metalloproteinase 7 as a Diagnostic and Prognostic Biomarker for Extrahepatic Biliary Atresia

Teg Rabab Singh et al. J Indian Assoc Pediatr Surg. 2022 Mar-Apr.

Abstract

Background: Differentiation of neonatal cholestasis into neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA) is essential to formulate the treatment plan; promptness is indispensable for optimal outcomes. The clinical and nonoperative algorithms lack precision; the gold standard investigations (liver biopsy or per-operative cholangiogram) are invasive. There is a need for a noninvasive test which is both, sensitive and specific and has a high likelihood ratio.

Aim: To study the (diagnostic) role of matrix metalloproteinase 7 (MMP-7) as a serum biomarker to differentiate between EHBA and NH and evaluate the prognostic significance in EHBA based on its correlation with liver histopathology and serological predictors of liver fibrosis - Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4).

Materials and methods: This was a prospective study conducted upon patients of neonatal cholestasis presenting with acholic stools (n = 46) with equal number of controls (n = 45) with no liver pathology. Observational parametric included disease-specific workup and serum MMP-7 levels (all participants); liver biopsyl and APRI-FIB-4 (EHBA).

Results: (Diagnostic) Serum MMP-7 levels were significantly elevated in EHBA (n = 25; 28 ng/mL) as compared to those in NH (n = 21; 1.88 ng/mL) and normal infants (n = 45; 1.2 ng/mL) (P < 0.001 for both). Serum cutoff at 4.99 ng/mL differentiated EHBA-NH with a high sensitivity (96%), specificity (90.5%), and a negative predictive value (95%), with the number needed to misdiagnose being 23. (Prognostic) Inflammatory activity and fibrosis-stage on liver histopathology (METAVIR-and-Ishak scores) correlated with MMP-7 levels. APRI and FIB-4 scores also depicted a strong correlation with each other, age of the patient, and liver fibrosis.

Conclusions: MMP-7 has a diagnostic value in differentiating EHBA from NH and may also be used as a prognostic biomarker in the follow-up of these patients. MMP-7 levels in controls may be used as a baseline for future studies.

Keywords: Aspartate-to-Platelet Ratio Index; Fibrosis-4; Ishak scoring; METAVIR scoring; matrilysin; matrix metalloproteinase 7; neonatal cholestasis; neonatal hepatitis; serum biomarker.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Box-and-Whisker plot depicting the distribution of matrix metalloproteinase 7 (ng/mL) in patients with extrahepatic biliary atresia and neonatal hepatitis and in control participants. The middle horizontal line represents the median matrix metalloproteinase 7 (ng/mL) and the upper and lower bounds of the box represent the 75th and the 25th centile of matrix metalloproteinase 7 (ng/mL), respectively
Figure 2
Figure 2
Receiver-operator characteristic curve analysis showing diagnostic performance of matrix metalloproteinase 7 (ng/mL) in predicting extrahepatic biliary atresia (n = 25) versus neonatal hepatitis (n = 21)
Figure 3
Figure 3
Receiver-operator characteristic curve analysis showing diagnostic performance of matrix metalloproteinase 7 (ng/mL) in predicting neonatal hepatitis (n = 21) versus controls (n = 45)
Figure 4
Figure 4
Correlation between serum matrix metalloproteinase 7 levels (ng/mL) and inflammatory activity in the liver (Ishak scale 0–18)
See this image and copyright information in PMC

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