Relationship between intrahepatic bile duct development and hepatic fibrosis in children with biliary dysplasia

Abstract

Objective To explore the pathological changes of intrahepatic bile duct development and liver fibrosis in children with biliary dysplasia at different ages and to explore the effect of intrahepatic bile duct development on liver fibrosis. Methods From January 2015 to January 2019, a total of 16 hospitalized children with biliary dysplasia at Municipal Children's Hospital and First Central Municipal Hospital were recruited and divided into two groups according to age, i. e. <180 days (G1, n=8) and ≥180 days (G2, n=8). Liver biopsy specimens were harvested intraoperatively for routine hematoxylin & eosin and immunohistochemical staining (CK19 & EMA). The major histopathological changes of liver, such as ratio of interlobular bile duct to portal area, diameter of interlobular bile duct, ductal proliferation, liver fibrosis, cholestasis, bile plugs in ductules and an infiltration of inflammatory cells in portal region, were analyzed. Results The pathological changes of G1 and G2 groups showed that the degree of liver fibrosis in G2 group was higher than that in G1 group [0.5(0, 1) vs. 4(2.25, 4)]. The inter-group difference was statistically significant (Z=3.467, P<0.001); The ratio of interlobular bile duct to portal area was lower in G2 group than that in G1 group [0.25(0.16, 0.34) vs. 0]. The inter-group difference was statistically significant (Z=2.663, P<0.05); The degree of ductal proliferation showed that G2 group was significantly higher than G1 group [1(0.25, 2) vs. 2.5(2, 3.75)]. The inter-group difference was statistically significant (Z=2.867, P<0.05). The expression of EMA was significantly lower in G2 group than that in G1 group [(0.034±0.012) vs. (0.082±0.009)]. The inter-group difference was statistically significant (t=9.432, P<0.001); The expression of CK19 was significantly higher in G2 group than that in G1 group [(0.201±0.016) vs. (0.135±0.010)]. There was significant inter-group difference (t=9.615, P<0.001). Correlation analysis of intrahepatic bile duct development revealed: ratio of interlobular bile duct to portal area and age of children (rs=-0.714, P=0.002), ductal proliferation (rs=-0.610, P=0.012) and liver fibrosis (rs=-0.533, P<0.05) showed a significant negative correlation. Conclusions With the aging of the patients, interlobular bile duct of children with biliary dysplasia decreases gradually. And the degree of hepatic fibrosis continues aggravating with a poor prognosis. Key words: Hepatic fibrosis; Interlobular bile duct; Deficiency symptom; Bile duct; Hyperplasia