Deep learning quantification reveals a fundamental prognostic role for ductular reaction in biliary atresia.

Autor:	Nyholm I; Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children and Adolescent Department, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Pediatric Research Center, Children and Adolescent Department, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Sjöblom N; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Pihlajoki M; Pediatric Research Center, Children and Adolescent Department, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Hukkinen M; Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children and Adolescent Department, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Lohi J; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Heikkilä P; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Mutka A; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Jahnukainen T; Department of Pediatric Nephrology and Transplantation, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Davenport M; Department of Pediatric Surgery, King's College Hospital, London, UK., Heikinheimo M; Pediatric Research Center, Children and Adolescent Department, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.; Department of Pediatrics, Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Arola J; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Pakarinen MP; Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children and Adolescent Department, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Pediatric Research Center, Children and Adolescent Department, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Hepatology communications [Hepatol Commun] 2023 Dec 01; Vol. 7 (12). Date of Electronic Publication: 2023 Dec 01 (Print Publication: 2023).
DOI:	10.1097/HC9.0000000000000333
Abstrakt:	Background: We aimed to quantify ductular reaction (DR) in biliary atresia using a neural network in relation to underlying pathophysiology and prognosis. Methods: Image-processing neural network model was applied to 259 cytokeratin-7-stained native liver biopsies of patients with biliary atresia and 43 controls. The model quantified total proportional DR (DR%) composed of portal biliary epithelium (BE%) and parenchymal intermediate hepatocytes (PIH%). The results were related to clinical data, Sirius Red-quantified liver fibrosis, serum biomarkers, and bile acids. Results: In total, 2 biliary atresia biopsies were obtained preoperatively, 116 at Kasai portoenterostomy (KPE) and 141 during post-KPE follow-up. DR% (8.3% vs. 5.9%, p=0.045) and PIH% (1.3% vs. 0.6%, p=0.004) were increased at KPE in patients remaining cholestatic postoperatively. After KPE, patients with subsequent liver transplantation or death showed an increase in DR% (7.9%-9.9%, p = 0.04) and PIH% (1.6%-2.4%, p = 0.009), whereas patients with native liver survival (NLS) showed decreasing BE% (5.5%-3.0%, p = 0.03) and persistently low PIH% (0.9% vs. 1.3%, p = 0.11). In Cox regression, high DR predicted inferior NLS both at KPE [DR% (HR = 1.05, p = 0.01), BE% (HR = 1.05, p = 0.03), and PIH% (HR = 1.13, p = 0.005)] and during follow-up [DR% (HR = 1.08, p<0.0001), BE% (HR = 1.58, p = 0.001), and PIH% (HR = 1.04, p = 0.008)]. DR% correlated with Sirius red-quantified liver fibrosis at KPE (R = 0.47, p<0.0001) and follow-up (R = 0.27, p = 0.004). A close association between DR% and serum bile acids was observed at follow-up (R = 0.61, p<0.001). Liver fibrosis was not prognostic for NLS at KPE (HR = 1.00, p = 0.96) or follow-up (HR = 1.01, p = 0.29). Conclusions: DR predicted NLS in different disease stages before transplantation while associating with serum bile acids after KPE. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)
Databáze:	MEDLINE
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