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Biliary atresia

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Abstract

Biliary atresia (BA) is a progressive inflammatory fibrosclerosing disease of the biliary system and a major cause of neonatal cholestasis. It affects 1:5,000–20,000 live births, with the highest incidence in Asia. The pathogenesis is still unknown, but emerging research suggests a role for ciliary dysfunction, redox stress and hypoxia. The study of the underlying mechanisms can be conceptualized along the likely prenatal timing of an initial insult and the distinction between the injury and prenatal and postnatal responses to injury. Although still speculative, these emerging concepts, new diagnostic tools and early diagnosis might enable neoadjuvant therapy (possibly aimed at oxidative stress) before a Kasai portoenterostomy (KPE). This is particularly important, as timely KPE restores bile flow in only 50–75% of patients of whom many subsequently develop cholangitis, portal hypertension and progressive fibrosis; 60–75% of patients require liver transplantation by the age of 18 years. Early diagnosis, multidisciplinary management, centralization of surgery and optimized interventions for complications after KPE lead to better survival. Postoperative corticosteroid use has shown benefits, whereas the role of other adjuvant therapies remains to be evaluated. Continued research to better understand disease mechanisms is necessary to develop innovative treatments, including adjuvant therapies targeting the immune response, regenerative medicine approaches and new clinical tests to improve patient outcomes.

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Fig. 1: Global incidence of biliary atresia.
Fig. 2: Aetiological heterogeneity of biliary atresia.
Fig. 3: BA as a combination of injury and maladaptive response.
Fig. 4: Hypothetical contribution of immune dysregulation to the pathogenesis of biliary atresia.
Fig. 5: Kasai portoenterostomy.
Fig. 6: Potential regenerative strategies in biliary atresia treatment.
Fig. 7: Postoperative follow-up of native liver survivors.
Fig. 8: Future research directions and effects on patient outlook.

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Acknowledgements

P.K.H.T., C.S.M.T. and V.C.H.L. disclose funding support for the research for this work from the Theme-based Research Scheme (T12-712/21-R), CERG (17105119), HMRF (09201836) and Commissioned HMRF (PR-HKU-1) from the Hong Kong SAR Government; P.K.H.T. was also supported by Macau FDCT0011/2023/AKP. R.G.W. was supported by NIH R01 DK119290 and the Children’s Hospital of Philadelphia-Fred and Suzanne Biesecker Paediatric Liver Center.

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Authors and Affiliations

  1. Medical Sciences Division, Macau University of Science and Technology, Macau, China

    Paul K. H. Tam

  2. Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Paul K. H. Tam, Clara S. M. Tang & Vincent C. H. Lui

  3. Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Rebecca G. Wells

  4. Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong SAR, China

    Clara S. M. Tang & Vincent C. H. Lui

  5. Section of Paediatric Surgery, Paediatric Liver and Gut Research Group, New Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

    Maria Hukkinen & Mikko Pakarinen

  6. Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

    Carlos D. Luque

  7. NIHR Biomedical Research Centre, Great Ormond Street Hospital for Children NHS Foundation Trust and Great Ormond Street Institute of Child Health, University College London, London, UK

    Paolo De Coppi

  8. Department of Paediatrics, Division of Paediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Children’s Wisconsin, Milwaukee, WI, USA

    Cara L. Mack

  9. Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden

    Mikko Pakarinen

  10. Department of Paediatric Surgery, King’s College Hospital, London, UK

    Mark Davenport

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Contributions

Introduction (P.K.H.T.); Epidemiology (P.K.H.T. and M.H.); Mechanisms/pathophysiology (P.K.H.T., C.S.M.T., V.C.H.L., C.L.M. and R.G.W.); Diagnosis, screening and prevention (P.K.H.T., M.D., C.D.L. and M.P.); Management (P.K.H.T., M.D., P.D.C. and M.P.); Quality of life (P.K.H.T. and M.P.); Outlook (P.K.H.T. and P.D.C.); overview of the Primer (P.K.H.T.).

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Correspondence to Paul K. H. Tam.

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Nature Reviews Disease Primers thanks D. A. Kelly; A. Miethke, who co-reviewed with A. Russi; H. Verkade; and A. Yamataka for their contribution to the peer review of this work.

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Tam, P.K.H., Wells, R.G., Tang, C.S.M. et al. Biliary atresia. Nat Rev Dis Primers 10, 47 (2024). https://doi.org/10.1038/s41572-024-00533-x

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