Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia

Abstract

Objectives: Matrix metallopeptidase-7 (MMP-7) and osteopontin (OPN) are important components in the pathophysiology of fibrosis in biliary atresia (BA). There has been much recent interest in MMP-7 serum level in the diagnosis of BA. We aimed to assess the diagnostic accuracy and prognostic value of both MMP-7 and OPN in a Western BA study. Methods: Diagnostic value was assessed by comparison of serum MMP-7 and OPN levels in infants with BA and age-matched cholestatic controls. Prognostic value was assessed through subsequent clearance of jaundice (COJ) and need for liver transplantation (LT). Results: Serum was assessed from 32 BA and 27 controls. Median MMP-7 was higher in BA (96.4 vs 35 ng/mL; P < 0.0001) with an optimal cut-off value of 69 ng/mL. Sensitivity and specificity was 68% and 93%, respectively [negative predictive value (NPV) = 71%]. Similarly, median OPN was higher in BA (1952 vs 1457 ng/mL; P = 0.0001) and an optimal cut-off of 1611 ng/mL. Sensitivity and specificity was 84% and 78%, respectively (NPV = 81%). MMP-7 level correlated positively with Ishak liver fibrosis score (r = 0.27, P = 0.04). Neither MMP-7 (70 vs 100 ng/mL; P = 0.2) nor OPN (1969 vs 1939 ng/mL; P = 0.3) were predictive of COJ, or need for LT (99 vs 79 ng/mL; P = 0.7, and 1981 vs 1899 ng/mL; P = 0.2), respectively. Conclusions: MMP-7 and OPN may have contributory value in the diagnosis of BA, but remain far of the "gold standard" role. Much more prospective data are required and collaborative multi-center initiatives should be the next logical steps.

Progress in Biomarkers Related to Biliary Atresia

“…A recent study in the UK has shown that MMP-7 may also hold significance in the diagnosis of BA among Western patients. 38 However, we found the sensitivity of MMP-7 in the diagnosis of BA was much lower in Western studies than in Asian studies, and the cutoff value was much higher. In addition to the use of different ELISA kits, this may also reflect ethnic differences in BA.…”

“…The results of some important clinical studies on MMP-7 from 2018 to 2023 are shown in Table 1. [31][32][33][34][35][36][37][38][39][40] According to the systematic review by He et al, 31 the sensitivity, specificity, and area under the curve of MMP-7 in the diagnosis of BA were 96%, 91%, and 0.9847, respectively. It is worth noting that the studies by Jiang et al 32 and Yang et al 33 were comparable, because they used the same enzyme-linked immunosorbent assay (ELISA) kit to detect serum MMP-7 concentration, both were conducted in China, and the median ages of the patients in the BA group were similar in the two studies.…”

Expedited Laparoscopic Cholangiogram and Liver Biopsy in the Workup of Biliary Atresia

“…They found the specificity and sensitivity of MMP-7 in the diagnoses of BA to be 68% and 93%, respectively, with a negative predictive value of 71% (27). They further conclude that MMP-7 may be helpful in the diagnosis of BA, but it is far from a new diagnostic "gold standard" (27). Surgical consultation may be delayed given the hesitancy from pediatric teams due to perceived morbidity of surgical intervention (28).…”

“…Aldeiri et al recently conducted a single center study at a referral hospital in the United Kingdom to better define the role of MMP-7 in the diagnoses of BA. They found the specificity and sensitivity of MMP-7 in the diagnoses of BA to be 68% and 93%, respectively, with a negative predictive value of 71% (27). They further conclude that MMP-7 may be helpful in the diagnosis of BA, but it is far from a new diagnostic “gold standard” (27).…”

“…They found the specificity and sensitivity of MMP‐7 in the diagnoses of BA to be 68% and 93%, respectively, with a negative predictive value of 71% (27). They further conclude that MMP‐7 may be helpful in the diagnosis of BA, but it is far from a new diagnostic “gold standard” (27).…”