Predicting native liver injury and survival in biliary atresia

Several patient and treatment related factors significantly modify outcomes of biliary atresia. The extremely variable prognosis mandates intensive postoperative monitoring following portoenterostomy. Accurate prediction of outcome and progression of liver injury would enable individualized treatment and follow-up protocols, patient counseling and meaningful stratification of patients into clinical trials. While results on most biomarkers of cholestasis, hepatocyte function, fibrosis and inflammation studied so far are inconsistent or have not been validated in independent patient cohorts, postoperative serum bilirubin level 3 months after portoenterostomy remains the most accurate clinically feasible predictor of native liver survival. Although liver stiffness and a novel marker of cholangiocyte integrity, serum matrix metalloproteinase-7, correlate with liver fibrosis and may discriminate biliary atresia from other causes of neonatal cholestasis, further information on their ability to predict portoenterostomy outcomes is needed. Recent gene expression profiling has shown promise in overcoming the sampling error associated with histological quantification of liver fibrosis, and provides an important possibility to stratify patients for clinical trials according to the prognosis of native liver survival already preoperatively. As activity and extent of ductular reaction is linked with progression of liver fibrosis in cholangiopathies, further research is also warranted to evaluate predictive value of ductular reaction, matrix metalloproteinase-7 and the underlying gene expression signatures in relation to circulating bile acids in biliary atresia. Discovery of accurate predictive tools will ultimately increase our understanding of the unpredictable response to surgery and pathophysiology of progressive liver injury in biliary atresia.