Serum matrix metalloproteinase 7 as a diagnostic and prognostic biomarker for extrahepatic biliary atresia
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 investig...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2022-01-01
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| Series: | Journal of Indian Association of Pediatric Surgeons |
| Subjects: | |
| Online Access: | http://www.jiaps.com/article.asp?issn=0971-9261;year=2022;volume=27;issue=2;spage=227;epage=235;aulast=Singh |
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| author | Teg Rabab Singh Prabudh Goel Minu Bajpai Devasenathipathy Kandasamy Rohan Malik Rajni Yadav Shyam Prakash Kalaivani Mani Madhavi Tripathi Devendra Kumar Yadav Anjan Kumar Dhua Vishesh Jain Sandeep Agarwala |
| author_facet | Teg Rabab Singh Prabudh Goel Minu Bajpai Devasenathipathy Kandasamy Rohan Malik Rajni Yadav Shyam Prakash Kalaivani Mani Madhavi Tripathi Devendra Kumar Yadav Anjan Kumar Dhua Vishesh Jain Sandeep Agarwala |
| author_sort | Teg Rabab Singh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T19:19:38Z |
| format | Article |
| id | doaj.art-ecedf5e0403a4747b479f0c19b441afb |
| institution | Directory Open Access Journal |
| issn | 0971-9261 1998-3891 |
| language | English |
| last_indexed | 2024-04-13T19:19:38Z |
| publishDate | 2022-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Journal of Indian Association of Pediatric Surgeons |
| spelling | doaj.art-ecedf5e0403a4747b479f0c19b441afb2022-12-22T02:33:34ZengWolters Kluwer Medknow PublicationsJournal of Indian Association of Pediatric Surgeons0971-92611998-38912022-01-0127222723510.4103/jiaps.JIAPS_389_20Serum matrix metalloproteinase 7 as a diagnostic and prognostic biomarker for extrahepatic biliary atresiaTeg Rabab SinghPrabudh GoelMinu BajpaiDevasenathipathy KandasamyRohan MalikRajni YadavShyam PrakashKalaivani ManiMadhavi TripathiDevendra Kumar YadavAnjan Kumar DhuaVishesh JainSandeep AgarwalaBackground: 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.http://www.jiaps.com/article.asp?issn=0971-9261;year=2022;volume=27;issue=2;spage=227;epage=235;aulast=Singhaspartate-to-platelet ratio indexfibrosis-4ishak scoringmatrilysinmatrix metalloproteinase 7metavir scoringneonatal cholestasisneonatal hepatitisserum biomarker |
| spellingShingle | Teg Rabab Singh Prabudh Goel Minu Bajpai Devasenathipathy Kandasamy Rohan Malik Rajni Yadav Shyam Prakash Kalaivani Mani Madhavi Tripathi Devendra Kumar Yadav Anjan Kumar Dhua Vishesh Jain Sandeep Agarwala Serum matrix metalloproteinase 7 as a diagnostic and prognostic biomarker for extrahepatic biliary atresia Journal of Indian Association of Pediatric Surgeons aspartate-to-platelet ratio index fibrosis-4 ishak scoring matrilysin matrix metalloproteinase 7 metavir scoring neonatal cholestasis neonatal hepatitis serum biomarker |
| title | Serum matrix metalloproteinase 7 as a diagnostic and prognostic biomarker for extrahepatic biliary atresia |
| title_full | Serum matrix metalloproteinase 7 as a diagnostic and prognostic biomarker for extrahepatic biliary atresia |
| title_fullStr | Serum matrix metalloproteinase 7 as a diagnostic and prognostic biomarker for extrahepatic biliary atresia |
| title_full_unstemmed | Serum matrix metalloproteinase 7 as a diagnostic and prognostic biomarker for extrahepatic biliary atresia |
| title_short | Serum matrix metalloproteinase 7 as a diagnostic and prognostic biomarker for extrahepatic biliary atresia |
| title_sort | serum matrix metalloproteinase 7 as a diagnostic and prognostic biomarker for extrahepatic biliary atresia |
| topic | aspartate-to-platelet ratio index fibrosis-4 ishak scoring matrilysin matrix metalloproteinase 7 metavir scoring neonatal cholestasis neonatal hepatitis serum biomarker |
| url | http://www.jiaps.com/article.asp?issn=0971-9261;year=2022;volume=27;issue=2;spage=227;epage=235;aulast=Singh |
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