Quantification of Serum Matrix Metallopeptide 7 Levels May Assist in the Diagnosis and Predict the Outcome for Patients with Biliary Atresia

Wu, Jia‐Feng; Jeng, Yung‐Ming; Chen, Huey‐Ling; Ni, Yen‐Hsuan; Hsu, Hong–Yuan

doi:10.1016/j.jpeds.2018.12.006

Cited by 65 publications

(100 citation statements)

References 37 publications

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“…[30][31][32] Moreover, recent diagnostic tests have further confirmed its diagnostic accuracy as a biomarker for BA. 27,28 However, a cutoff value has not been agreed on at present.…”

Section: Discussionmentioning

confidence: 99%

“…The area under the curve (AUC) was 0.99 with a sensitivity, specificity, and PPV of 98.67%, 95%, and 98.28%, respectively. 27 However, most recently, Wu et al 28 found that a serum MMP-7 level of .1.43 ng/mL was predictive of BA in infants with cholestasis with a sensitivity of 97.30% and a specificity of 83.20%. The cutoff value was different in the 2 studies, although the patients were all from a Chinese cohort.…”

Section: What This Study Addsmentioning

confidence: 99%

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Serum MMP-7 in the Diagnosis of Biliary Atresia

et al. 2019

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BACKGROUND: The overlapping features of biliary atresia (BA) and other neonatal cholestasis with alternative causes (non-BA) have posed challenges for diagnosis. Matrix metalloproteinase-7 (MMP-7) has been reported to be promising in diagnosing BA. We aimed to validate the diagnostic accuracy of MMP-7 for BA in a large population sample. METHODS: We enrolled 288 patients with neonatal obstructive jaundice from March 2017 to October 2018. Serum MMP-7 levels were measured by using an enzyme-linked immunosorbent assay. Receiver operating characteristic curves were constructed, and decision curve analysis was done. A Pearson correlation coefficient test was conducted to assess the correlation between MMP-7 levels and other characteristics. RESULTS: The median serum MMP-7 levels were 38.89 ng/mL (interquartile range: 22.96-56.46) for the BA group and 4.4 ng/mL (interquartile range: 2.73-6.56) for the non-BA group (P , .001). The area under the receiver operating characteristic curve value was 0.9829 for MMP-7, and the sensitivity, specificity, positive predictive value, and negative predictive value were 95.19%, 93.07%, 97.27%, and 91.43%, respectively, at a cutoff value of 10.37 ng/mL. When MMP-7 was combined with g glutamyl transferase, the diagnostic accuracy was slightly improved without significance when compared with MMP-7 alone and had an area under the curve of 0.9880 (P = .08). Decision curve analysis also showed potential for MMP-7 to be used for clinical applications. A significant correlation was found with fibrosis stage from liver biopsy (R = 0.47; P , .001). CONCLUSIONS: MMP-7 demonstrated good accuracy in diagnosing BA and holds promise for future clinical application. Furthermore, its correlation with liver fibrosis indicated its potential use as a therapeutic target or prognostic biomarker.

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“…[30][31][32] Moreover, recent diagnostic tests have further confirmed its diagnostic accuracy as a biomarker for BA. 27,28 However, a cutoff value has not been agreed on at present.…”

Section: Discussionmentioning

confidence: 99%

Section: What This Study Addsmentioning

confidence: 99%

Serum MMP-7 in the Diagnosis of Biliary Atresia

et al. 2019

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“…n Off-Label Drugs in Neonatology: Analyses Using Large Data Bases T wo reports in this volume of The Journal from the neonatology team at the University of North Carolina use the Pediatrix Medical Group Data Warehouse of administrative information to further the ongoing discussion of the frequent off-label uses of drugs in the neonatal intensive care unit (NICU). 1,2 The report on the frequent, but not approved, use of furosemide for bronchopulmonary dysplasia (BPD) identified that prolonged use can decrease BPD. 1 The report on surfactant for preterm infants with or at risk of respiratory distress syndrome (RDS) identified frequent deviations from the Food and Drug Administration (FDA) approved uses.…”

Section: Mmp-7mentioning

confidence: 99%

“…1,2 The report on the frequent, but not approved, use of furosemide for bronchopulmonary dysplasia (BPD) identified that prolonged use can decrease BPD. 1 The report on surfactant for preterm infants with or at risk of respiratory distress syndrome (RDS) identified frequent deviations from the Food and Drug Administration (FDA) approved uses. 2 The term off-label is frequently loosely used without precision as to its definition.…”

Section: Mmp-7mentioning

confidence: 99%

“…Wu et al confirm the diagnostic utility of serum MMP-7 levels. 1 They studied 100 cholestatic infants presenting consecutively to their institution over a 10-year period, including 36 eventually diagnosed with biliary atresia. Median serum MMP-7 levels were significantly higher in biliary atresia at the time of diagnosis, with an optimal serum MMP-7 level of >1.43 ng/mL for predicting biliary atresia.…”

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confidence: 99%

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MMP-7: The Next Best Serum Biomarker for Biliary Atresia?

Harpavat

2019

The Journal of Pediatrics

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Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease

Devaraj¹,

Goodrich²,

Chen³

et al. 2022

Hepatology

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Background and Aims: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. Approach and Results: A targeted enzyme‐linked immunosorbent assay–based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL‐8, endoglin, periostin, Mac‐2–binding protein, MMP‐3, and MMP‐7) was examined in children with biliary atresia (BA; n = 187), alpha‐1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin (p = 0.04) and IL‐8 (p < 0.001) and MMP‐7 (p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R 2 = 0.437; adding IL‐8 and MMP‐7 improved R 2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated (p = 0.004); adding CTGF to an LSM prediction model improved R 2 from 0.524 to 0.577 (p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. Conclusions: Endoglin, IL‐8, and MMP‐7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease‐specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.

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Quantification of Serum Matrix Metallopeptide 7 Levels May Assist in the Diagnosis and Predict the Outcome for Patients with Biliary Atresia

Cited by 65 publications

References 37 publications

Serum MMP-7 in the Diagnosis of Biliary Atresia

Serum MMP-7 in the Diagnosis of Biliary Atresia

MMP-7: The Next Best Serum Biomarker for Biliary Atresia?

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease

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