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Bile UPLC-MS fingerprinting and bile acid fluxes during human liver transplantation

Authors

  • Cristina Legido-Quigley,

    Corresponding author
    1. Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
    2. Institute of Pharmaceutical Science, School of Biomedical and Health Sciences, King's College London, London, United Kingdom
    • Biomolecular Medicine, Department of Surgery and Cancer, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, SW7 2AZ, UK
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  • Lindsay McDermott,

    1. Institute of Pharmaceutical Science, School of Biomedical and Health Sciences, King's College London, London, United Kingdom
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  • Hector Vilca-Melendez,

    1. King's College Hospital, Liver Transplant Surgical Service, London, United Kingdom
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  • Gerard M. Murphy,

    1. Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
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  • Nigel Heaton,

    1. King's College Hospital, Liver Transplant Surgical Service, London, United Kingdom
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  • John C. Lindon,

    1. Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
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  • Jeremy K. Nicholson,

    1. Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
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  • Elaine Holmes

    1. Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
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  • Colour Online: See the article online to view Figs. 2–6 in colour.

Abstract

Bile flow restoration is a crucial step in the recovery process post transplantation of the liver. Here, metabolic trajectories based on changes in bile secretion – a known marker of functionality – have been utilised as an approach for discovering bile fluxes during transplantation. A total of ten liver transplants were monitored and from these 68 bile samples from both donors and recipients were collected and analysed using ultra-performance LC-MS in combination with multivariate statistical analysis. Based on the principal component scores constructed from the total bile fingerprint, differentiation of the bile acid concentrations before and after transplantation was detected. A trend was also observed, by constructing metabolic trajectories, whereby the post-transplant profiles approached the position of pre-transplant profiles within 30–60 min of the restoration of bile secretion function. The ten major conjugated bile acid salts were measured and a significant increase in concentrations of taurocholic acid and taurochenodeoxycholic acid were seen after transplantation. In addition, the ratios of secondary bile acids detected in gall bladder and hepatic bile were measured before and after transplantation. This study suggests that bile acid ratios in the donor liver at the pre-transplant and post-transplant stage may be important and that profiling of secreted bile after transplantation may aid clinical assessment and progress post-transplantation.

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