Dynamic analysis of serum MMP-7 and its relationship with disease progression in biliary atresia: a multicenter prospective study.

Abstract

We aimed to assess the dynamic changing trend of serum matrix metalloproteinase-7 (MMP-7) in biliary atresia (BA) patients from diagnosis to LTx to further elucidate its clinical value in diagnosis and prognoses and its relationship with disease progression. In this multicentre prospective study, 440 cholestasis patients (direct bilirubin level of > 17μmol/L) were enrolled. Serum MMP-7 levels were measured using an enzyme-linked immunosorbent assay at diagnosis, 1week, 2weeks, 1month, 6weeks, 2months, 3months, 6months and then every 6months post-KPE. The medical record at each follow-up visit for post-Kasai portoenterostomy patient was collected and analyzed. Using a cut-off value of > 26.73ng/mL, serum MMP-7 had an AUC of 0.954 in BA neonates and 0.983 in BA infants. A genetic mutation (G137D) was associated with low MMP-7 levels in serum of BA patients. MMP-7 showed a mediation effect on the association between inflammation and liver fibrosis in BA patients. Four dynamic patterns of serum MMP-7 post-KPE were associated with prognosis. Serum MMP-7 was the only significant predictor at 6weeks post-KPE and the most accurate predictor at 3months post-KPE of survival with the native liver in 2years. 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.