endothelin-1 and Biliary-Atresia

Biliary atresia (BA) is a severe neonatal liver disease characterized by progressive extrahepatic biliary tract and intrahepatic inflammatory process. Hepatic fibrosis and portal hypertension (PH) still occur despite the disappearance of jaundice following successful hepatic portoenterostomy. Endothelin-1 (ET-1) is a potent vasoconstrictor and has been reported to stimulate hepatic collagen synthesis. The aim of this study was to demonstrate the potential role of ET-1 in the pathogenesis of the progressive inflammation, fibrosis and PH in BA.. Thirty pediatric patients with biliary atresia post-hepatic portoenterostomy and 12 healthy children were examined. The ET-1 level was determined by commercially available enzyme-linked immunosorbent assay kits.. Endothelin-1 levels were elevated in the patients compared with those of the controls (5.45+/-3.34 vs. 2.74+/-2.17 pg/ml, P = 0.01). Moreover, patients with PH also had greater levels of ET-1 than those without PH (6.73+/-3.27 vs. 3.26+/-2.2 pg/ml, P = 0.004). Patients with abnormal transaminase enzymes had significantly higher ET-1 levels than those with normal enzymes (6.43+/-3.33 vs. 3.17+/-2.1 pg/ml, P = 0.01). In the jaundice-free group, endothelin-1 levels were elevated in the patients with PH compared with those without PH (5.93+/-2.15 vs. 2.88+/-2.1 pg/ml, P = 0.02).. Our findings showed elevation of plasma ET-1 levels in patients with BA, especially in those with PH. ET-1 levels were also higher in patients with elevated transminase enzymes as well as in the jaundice-free group with PH. ET-1 might play a role in the pathogenesis of the progressive inflammation, fibrosis and PH in BA.

Topics: Biliary Atresia; Child; Child, Preschool; Disease Progression; Endothelin-1; Female; Fibrosis; Humans; Hypertension, Portal; Infant; Male

The aim of this study was to examine if the plasma endothelin-1 (ET-1), a potent vasoconstrictor, level may reflect the severity of portal hypertension associated with liver cirrhosis in biliary atresia (BA).. Forty-eight postoperative BA patients aged 6 months to 20 years were studied. Plasma ET-1 was measured by a sandwich method of enzyme immunoassay. ET-1 was compared with Child's score and laboratory data. ET-1 levels were compared among groups of patients with various degrees of histologic fibrosis and portal hypertension.. Plasma ET-1 was 5.3 +/- 3.5 pg/mL in BA, higher than in controls (3.1 +/- 0.8, n = 27; P <.05). ET-1 correlated with Child's score, serum total bilirubin, direct bilirubin, aspartate aminotransferase, albumin, prothrombin time, hepaplastin test, fibrinogen, cholinesterase, total cholesterol, Fischer's molar ratio, prealubumin, and hyaluronic acid, respectively (P <.05). ET-1 also correlated with the severity of histologic fibrosis, gastroesophageal varices, the presence of splenomegaly, ascites, venous dilatation on the abdominal wall, or pulmonary vascular abnormalities. In 4 patients undergoing liver transplantation (LTx), ET-1 after LTx was lower than that before LTx (P <.05).. Plasma ET-1 level may be a useful index reflecting the severity of cirrhosis and portal hypertension in BA.

Topics: Adolescent; Adult; Biliary Atresia; Biomarkers; Child; Child, Preschool; Endothelin-1; Humans; Hypertension, Portal; Infant; Liver Cirrhosis; Portoenterostomy, Hepatic; Severity of Illness Index