High serum matrix metalloproteinase-3 and liver stiffness in postoperative biliary atresia

Abstract

Biliary atresia (BA) is a neonatal liver disorder characterized by chronic inflammation and obliteration of extrahepatic bile ducts. The purpose of the study was to investigate serum matrix metalloproteinase-3 (MMP-3) in postoperative BA patients and the association of MMP-3 with clinical outcome and liver stiffness score. Fifty-eight BA patients post-Kasai operation and 20 controls were enrolled. None of the patients had undergone liver transplantation. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (TB < 2 mg/dL, no jaundice vs. TB ≥ 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT) levels (ALT < 45 IU/L, normal ALT vs. ALT ≥ 45 IU/L, elevated ALT). Serum MMP-3 levels were determined by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by FibroScan. BA patients had greater MMP-3 levels (10.8 ± 1.0 vs. 7.9 ± 0.8 ng/mL, P = 0.02) and higher liver stiffness values than controls (29.7 ± 3.0 vs. 5.1 ± 0.5 kPa, P < 0.001). Serum MMP-3 levels were significantly elevated in BA patients with jaundice when compared with those without jaundice (15.3 ± 2.2 vs. 8.5 ± 0.8 ng/mL, P = 0.004). In addition, BA patients with elevated ALT had higher levels of serum MMP-3 than those with normal ALT (12.4 ± 1.5 vs. 8.3 ± 0.9 ng/mL, P = 0.02). Moreover, BA patients with portal hypertension displayed higher serum MMP-3 than those without portal hypertension (13.5 ± 1.5 vs. 7.4 ± 0.8 ng/mL, P = 0.001). There was also a correlation between serum MMP-3 and liver stiffness scores (r = 0.448, P ≤ 0.001). Serum MMP-3 was associated with hepatic dysfunction and liver stiffness in postoperative BA patients. Accordingly, MMP-3 could play a role in the pathophysiology of hepatic fibrosis in BA after Kasai operation.