Clinicopathological study in 80 patients with Biliary atresia treated by liver transplantation with and without prior Kasai portoenterostomy

Objectives: Biliary atresia (BA) is a non-hereditary disease, unknown in etiology and affecting 1/18.000 births in Europe. Kasai portoenterostomy (KPE) is performed immediately after diagnosis. Depending on the patient's condition, liver transplantation (LT) may be needed. Pathological features in the explant liver could be a combination between original features (BA itself) and secondary features (influence of KPE). For instance, a perihilar benign hepatic nodule reported in Asian long surviving BA cohorts, is considered as secondary to the KPE. Our aim was to further enhance understanding of BA pathology by comparing clinicopathological-and macroscopical features in 80 BA LT patients with and without previous KPE. Material and methods: We investigated 80 BA patients who underwent LT (median age at LT: 2.5 years, 4 months to 32 years) at Saint-Luc Hospitals between 2009 and 2017. Clinical information was obtained by patient's file. Macro- and microscopical aspects were reviewed by liver-specialized pathologist. Results: Forty-eight (60%) out of 80 BA patients underwent KPE before LT. Post-KPE patients were significantly earlier diagnosed (P=0.001), older age at the LT (p=0.024), a longer time between BA diagnosis and LT (p=0.001), and showed a lower total bilirubin level (p=0.031), a higher albumin level (p=0.003), cholangitis (p=0.003), and severe portal hypertension (p=0.035) compared to non-Kasai group. Pathologically, non-KPE group showed significantly higher occurence of extrahepatic bile ducts (P=0.013), bilirubinostasis (P=0.048), and giant cell transformation (P=0.041) compared to KPE-group. Macroscopically, 80 BA were classified into three groups, biliary plug group (n=37, 46.2%), non-biliary plug group (N=35, 43.8 %), and large nodular group (n=8, 10%). Bile plug group was defined as a case showing biliary plugs in perihilar location. Fifteen (40.5%) out of 37 bile plug group cases showed biloma as well bile plugs. Non-biliary plug group was defined as a case without biliary plug or biloma. Finally, large nodular group was defined as a case showing a large nodular lesion. Large nodules measured between 3.5 cm and 10 cm and their locations were always near perihilar area. Large nodular group all had post-KPE status and showed significantly older age at the time of LT, a longer time between time of diagnosis and time of LT, higher prevalence of left liver graft, and lower Total Bilirubin level, compared to the other two groups. Pathologically, a large nodular area showed preserved liver architecture, less fibrosis and less hepatocellular damage and inflammation, compared to non-nodular area. There was no sign of malignancy in the nodules. Large nodular group showed a significantly less bilirubinostasis (p=0.001), less ductal plate malformation (P=0.005) and less extravasation of bile (P=0.001), compared to the other groups. Conclusion: Explant livers of BA patients with previous KPE more frequently showed cholangitis and/or severe portal hypertension, and better liver function than without KPE. Our data confirmed that a benign hilar nodule was seen in long survived post-KPE BA patients with distinct clinicopathological features. Based on these aspects, possible pathogenesis of the large nodule could be better biliary drainage of the perihilar liver due to KPE