Decrease of post-portoenterostomy liver fibrosis in a nationally centralized cohort of biliary atresia patients

Background & aims: Despite representing the dominant pathology in biliary atresia (BA), little is known about dynamics of liver fibrogenesis following Kasai portoenterostomy (KPE). We analyzed clinical outcomes in relation to progression of native liver (NL) fibrosis in a national BA cohort undergoing standardized management and NL protocol follow-up biopsies. Methods: Prospectively collected NL liver biopsies, serum samples and liver stiffness measurements at 1-, 5-, 10-, and 15-years after KPE were analyzed with clinical data for all consecutive BA patients (n = 66) managed following national centralization during 2005–2024. Liver fibrosis was scored by two pathologists using Metavir fibrosis stage (MFS). Results: In total, 62 patients underwent KPE, 2 had primary liver transplantation (LT), and 2 received compassionate care. At KPE, median age was 54 (IQR 34–72) days, and median MFS 2 (2–3). 57 patients received postoperative steroids, 61 ursodeoxycholic acid and 62 antimicrobial cholangitis prophylaxis. After PE, 47 patients (76 %) normalized bilirubin (<20 μmol/l) within 2.5 (0.9–3.5) months. 10-year NL survival was 47 % (95%CI 34–63) and overall survival 92 % (95%CI 86–99) with 90 % (27/30) post-liver transplantation survival. In total, 103 biopsy pairs were obtained at KPE and during follow-up in 47 patients. 26 (25 %) follow-up biopsies among 19 (40 %) individual patients displayed 1–2 stages lower MFS at follow-up than at KPE. Patients with decreasing fibrosis were more likely (HR = 11.5, 95%CI = 1.51–87.0, P = 0.0182) to survive with NL. Decreasing fibrosis linked with clearance of jaundice and lower serum bilirubin levels throughout the follow-up. Conclusions: Decrease of histopathological liver fibrosis occurred in 40 % of BA patients following a successful KPE and associated with efficient and sustained resolution of cholestasis and superior long-term NL survival.