Aim of the study. To evaluate how liver histopathology correlates with follow-up clinical outcomes among biliary atresia (BA) patients surviving with their native liver.
Methods. In a national cohort of BA patients clearing their jaundice and surviving with their native liver for over five years (n=24), liver biopsies at portoenterostomy and at follow-up were analyzed for fibrosis (Metavir 0-4), cholestasis (scored 0-3), portal inflammation (0-3), and ductal reaction with cytokeratin 7 (CK7)-positive ductular proliferations (0-2) and associated periportal hepatocyte-cholangiocyte metaplasia (HCM, 0-4). Esophageal varices or spleen size >2 SD in association with thrombocytopenia was considered portal hypertension. “Good outcome” was defined as normal aspartate aminotransferase, bilirubin, prothrombin ratio, prealbumin, and platelets.
Main results. At median age of 8.8 (interquartile range 7.0-14.3) years, 29% of native liver survivors had biochemical good outcome and 58% portal hypertension. Comparison between portoenterostomy and follow-up biopsies showed increasing fibrosis (mean 2.30 vs. 3.05 p=0.005) and HCM (1.16 vs. 1.79, p=0.073) while decreasing inflammation (2.25 vs. 0.95, p<0.001) and cholestasis (2.00 vs. 0.10, p<0.001). However, patients fulfilling the good outcome criteria demonstrated decreasing HCM (0.83 vs. 0.00, p=0.025), stable fibrosis (2.33 vs. 2.29, p=ns) (Figure), and a greater decrease in portal inflammation scores during follow-up than others (-2.17 vs. -0.93 units, p=0.002). Absence of portal hypertension related with stable fibrosis (2.11 vs. 2.60, p=ns) and HCM (0.89 vs. 0.70, p=ns), while patients with portal hypertension showed both increasing fibrosis (2.45 vs. 3.21, p=0.015) and HCM (1.40 vs. 2.43, p=0.023). Increasing HCM and residual inflammation reflected follow-up fibrosis scores (r=0.676-0.724, p≤0.001) and associated with lower body weight (r=-0.529-0.606, p=0.010-0.029).Conclusions. Increasing HCM and residual portal inflammation reflect postoperative disease activity affecting the clinical outcomes among native liver survivors. Decreasing HCM and stable fibrosis segregated one third of native liver survivors with normal liver biochemistry.