Dynamic Analysis of Serum MMP-7 and Its Relationship with Disease Progression in Biliary Atresia: A Multicenter Prospective Study

Purpose: We aimed to assess the dynamic changing trend of serum matrix metalloproteinase-7 (MMP-7) in BA patients from diagnosis to LTx to further elucidate its clinical value in diagnosis and prognoses and its relationship with disease progression. Methods: In this multicentre prospective study, a total of 440 cholestasis patients (direct bilirubin level of > 17 μmol/L) were enrolled. Serum and stool MMP-7 levels were measured using an enzyme-linked immunosorbent assay at different time points and analysed. The polymorphism of MMP-7 was assessed to explore the possible reasons for the low value in BA patients. Results: : In neonate biliary atresia patients, using a cut-off value of > 26.73 ng/ml, serum MMP-7 had a AUC of 0.954. A genetic mutation (G137D) and rapid degradation of MMP-7 in serum samples could cause low MMP-7 levels in serum of BA patients. Four dynamic patterns of serum MMP-7 post-KPE were associated with prognosis. A high concentration of MMP-7 in the stool is linked to a decreased serum MMP-7 concentration. MMP-7 showed a mediation effect on the association between inflammation and liver fibrosis in BA patients. Serum MMP-7 was the only significant predictor at six weeks post-KPE and the most accurate predictor at three months post-KPE of survival with the native liver (SNL) in two years. Conclusion: : As one of the critical factors associated with BA occurrence and progression, serum MMP-7 can be used for early diagnosis of BA and post-KPE MMP-7 level is the earliest prognostic biomarker so far.