Matrix metalloproteinase 7 as a diagnostic biomarker of biliary atresia: A systematic review

Background

Biliary atresia (BA) is a disease of the intrahepatic or extrahepatic bile ducts with an unknown etiology. It presents in neonates with jaundice, clay-colored stool, and often hepatomegaly. Early diagnosis of the disease is pivotal for long-term prognosis. If the BA is left untreated, progressive liver cirrhosis and death can occur. Persisting jaundice in infants born at term should lead to further examination of liver diseases. A range of laboratory analyses is used, but none is specific for BA. In this review, we investigate whether the level of matrix metalloproteinase 7 (MMP-7) in serum can be used as an early diagnostic biomarker for BA.

Method

A systematic literature search of the PubMed database revealed the two terms “matrix metalloproteinase 7” and “biliary atresia”. A total of 24 articles were identified; these articles were screened, and eight articles were found to be relevant for this literature review, each describing an independent study.

Results

In all eight articles, the diagnostic cut-off values for serum MMP-7 in BA patients vs. non-BA patients were determined by receiver operating characteristic (ROC) curve analysis and by determining the area under the curve (AUC). The AUC ranged from 0.96 to 0.99. All studies had a sensitivity of 95 % or above and a specificity of 83 % or above. The cut-off values were discordant and ranged from 1.43 ng/ml to 52.85 ng/ml. The calculated positive likelihood ratio (PLR) varied from 5.66 to 21.86, and the negative likelihood ratio (NLR) varied from 0.01 to 0.05 among the eight studies. Finally, the diagnostic odds ratio (DOR) varied from 168.64 to 1406.00 in seven out of the eight studies.

Conclusion

The serum MMP-7 concentration can be used as a diagnostic biomarker according to the eight studies investigated in this review. However, further assessments of MMP-7 in larger, multicenter, and multiethnic studies are needed to validate its potential for biomarker development and, ultimately, its standard use in clinical practice.