Portal hypertension is a complication of children with biliary atresia. It results from progression of liver scarring (fibrosis) and can lead to gastrointestinal bleeding and accumulation of fluid in the abdomen (also known as ascites). In this study, investigations from the Childhood Liver Disease Research Network analyzed the blood of patients to identify protein that increase in children with portal hypertension. Investigators analyzed over 1,000 proteins using an assay known as proteomics. Among the proteins that increased in babies with portal hypertension they found that semaphorin 6B (SEMA6B) alone and three other protein combinations (SEMA6B+SFRP3, SEMA6B+COMMD7, and VCAM1+BMX) had high accuracy to identify portal hypertension. Analyzing liver biopsies, the new protein biomarkers showed increased expression in liver vascular cells (endothelial cells), bile duct epithelium (cholangiocytes), and immune cells within portal triads.
Large-scale proteomics identified SEMA6B, SFRP3, COMMD7, BMX, and VCAM1 as biomarkers highly associated with clinical portal hypertension in children with biliary atresia. The expression of the biomarkers in liver epithelial, endothelial, and immune cells support their potential role in the mechanisms that cause portal hypertension.