Serum matrix metalloproteinase‐7 in biliary atresia: A Japanese multicenter study

Abstract

Background Biliary atresia (BA) is among the commonest indications for liver transplantation (LT) in children. We examined whether serum matrix metalloproteinase‐7 (MMP‐7) is useful for diagnosis of BA in Japanese infants, and whether serum MMP‐7 concentrations before and after Kasai portoenterostomy (KP) predicted LT within a year. Methods Subjects under 6 months old at eight pediatric centers in Japan were enrolled retrospectively, including patients with cholestasis and normal controls (NC) without liver disease. Patients with cholestasis were divided into groups representing BA versus cholestasis from other causes (non‐BA). Serum samples were collected from patients with BA at diagnosis and 1 and 4 weeks after KP, as well as from non‐BA and NC. Results Serum MMP‐7 concentrations were significantly higher in BA at diagnosis (median, 89.1 ng/ml) than in non‐BA (11.0; p < 0.001) or NC (10.3; p < 0.001). Receiver operating characteristic (ROC) analysis of MMP‐7 for BA versus non‐BA yielded an area under the ROC curve of 0.99 (95% confidence interval, 0.96–1.00). An optimal cut‐off value of 18.6 ng/ml for serum MMP‐7 in diagnosing BA demonstrated sensitivity and specificity of 100% and 90%, respectively. Serum MMP‐7 before and 1 week and 4 weeks after KP did not differ significantly between BA requiring only KP and BA requiring LT after KP. Conclusion Serum MMP‐7 is a useful marker for diagnosis of BA in Japanese infants, but it could not predict LT within a year.

Serum matrix metalloproteinase-7 levels in infants with cholestasis and biliary atresia

“…The results also showed that the serum level of MMP-7 above 1.43 ng / ml was a predictor of biliary atresia in neonates with cholestasis (diagnostic accuracy, 88%) [ 3 ]. Recently, a retrospective study in Japan of individuals under 6 months of age showed that serum concentrations of MMP-7 were higher in BA at diagnosis (median, 89.1 ng / ml) than in non-BA (11.0) or healthy neonates (10.3) were significantly higher [ 19 ]. In addition, the area under the ROC curve for MMP-7 in BA versus non-BA subjects was 0.99 (95% confidence interval, 0.96–1.00).…”

“…In addition, the area under the ROC curve for MMP-7 in BA versus non-BA subjects was 0.99 (95% confidence interval, 0.96–1.00). However, the sensitivity and specificity at the optimal cut-off of 18.6 ng / ml for MMP-7 serum in the diagnosis of BA were 100 and 90%, respectively [ 19 ].…”

Summarization of the literature published on biliary atresia: a comprehensive literature review

“…Studies reported the high concentration of MMP-7, significant variation in VCAM-1, HLA-DRA and CD74 as a biomarker for the diagnosis of BA. [15][16][17] Tsuda et al suggested using 99m Tc-PMT scintigraphy as a diagnostic method of BA to differentiate BA and non-BA patients. Achieving high diagnostic accuracy the authors revealed the 99m Tc-PMT scintigraphy can produce better results compared to conventional methods.…”

“…12 Studies reported the high concentration of MMP-7 among BA patients and perhaps serves as a diagnostic parameter. 15,16 BA could be due to immune-related genes (IRGs) and can serve as a biomarker. 17 Li et al conducted a study in which they studied the role of IRGs in the occurrence of BA.…”

Meconium Peritonitis, Intestinal Atresia Combined With Biliary Atresia: A Case Report

“…A multicenter study conducted by Sakaguchi et al suggested that serum MMP-7 was a useful marker for the diagnosis of BA in Japanese infants. The optimal cut-off value was 18.6 ng/ml, and the sensitivity and specificity were 100 and 90%, respectively; however, serum MMP-7 could not predict liver transplantation (LT) within a year ( 12 ). Zhao et al ( 13 ) showed that GCDCA/CDCA can be used to assess the risk of BA in infants with cholestasis.…”