Fibrotic liver injury in biliary atresia: long-term implications

Normalization of serum bilirubin after Kasai portoenterostomy (KPE) is a prerequisite for long-term native liver (NL) survival. Following a successful KPE, fibrotic liver injury progresses variably, although a significant proportion of patients show decreasing histological liver fibrosis during follow-up. Eventually, the great majority of patients develop cirrhosis and clinical manifestations of portal hypertension (PH), while liver malignancies and pulmonary complications of PH occur infrequently. Accurate prediction of liver fibrosis remains challenging. Development of reliable noninvasive biomarkers of liver fibrosis would improve patient management and benefit performance of interventional trials. Although successful KPE modifies liver gene expression profile, molecular signature of active fibrogenesis and ductular reaction (DR) persists. Successful KPE reduces the abundance of activated myofibroblasts and macrophages, whereas cholangiocytes tend to increase. Progression of long-term fibrotic liver injury is tightly connected with DR, which is associated with serum bile acids. While serum bile acids are predictive of portal fibrosis and NL survival, there are ongoing randomized clinical trials evaluating the efficacy of bile acids lowering therapies on KPE outcomes. A better understanding of disease mechanisms underpinning progression of liver injury and clinical complications following successful KPE is needed for the development of novel adjuvant therapies, improvement of follow-up, and optimizing outcomes.