Biliary Bicarbonate, pH, and Glucose Are Suitable Biomarkers of Biliary Viability During Ex Situ Normothermic Machine Perfusion of Human Donor Livers

被引:138
|
作者
Matton, Alix P. M. [1 ,2 ]
de Vries, Yvonne [1 ,2 ]
Burlage, Laura C. [1 ,2 ]
van Rijn, Rianne [1 ,2 ]
Fujiyoshi, Masato [1 ]
de Meijer, Vincent E. [1 ]
de Boer, Marieke T. [1 ]
de Kleine, Ruben H. J. [1 ]
Verkade, Henkjan J. [3 ]
Gouw, Annette S. H. [4 ]
Lisman, Ton [2 ]
Porte, Robert J. [1 ]
机构
[1] Univ Med Ctr Groningen, Sect Hepatobiliary Surg & Liver Transplantat, Dept Surg, Groningen, Netherlands
[2] Univ Med Ctr Groningen, Dept Surg, Surg Res Lab, Groningen, Netherlands
[3] Univ Med Ctr Groningen, Sect Pediat Gastroenterol & Hepatol, Dept Pediat, Groningen, Netherlands
[4] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands
关键词
CARDIAC DEATH; BILE-DUCT; ISCHEMIC CHOLANGIOPATHY; CIRCULATORY-DEATH; COLD-STORAGE; TRANSPLANTATION; DONATION; PRESERVATION; INJURY; REOXYGENATION;
D O I
10.1097/TP.0000000000002500
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Ex situ normothermic machine perfusion (NMP) can be used to assess viability of suboptimal donor livers before implantation. Our aim was to assess the diagnostic accuracy of bile biochemistry for the assessment of bile duct injury (BDI). Methods. In a preclinical study, 23 human donor livers underwent 6 hours of end-ischemic NMP to determine biomarkers of BDI. Livers were divided into groups with low or high BDI, based on a clinically relevant histological grading system. During NMP, bile was analyzed biochemically and potential biomarkers were correlated with the degree of BDI. Receiver operating characteristics curves were generated to determine optimal cutoff values. For clinical validation, identified biomarkers were subsequently included as viability criteria in a clinical trial (n = 6) to identify transplantable liver grafts with low BDI. Results. Biliary bicarbonate and pH were significantly higher and biliary glucose was significantly lower in livers with low BDI, compared with high BDI. The following cutoff values were associated with low BDI: biliary bicarbonate greater than 18 mmol/L (P = 0.002), biliary pH greater than 7.48 (P = 0.019), biliary glucose less than 16 mmol/L (P = 0.013), and bile/perfusate glucose ratio less than 0.67 (P = 0.013). In the clinical trial, 4 of 6 livers met these criteria and were transplanted, and none developed clinical evidence of posttransplant cholangiopathy. Conclusions. Biliary bicarbonate, pH, and glucose during ex situ NMP of liver grafts are accurate biomarkers of BDI and can be easily determined point of care, making them suitable for the pretransplant assessment of bile duct viability. This may improve graft selection and decrease the risk of posttransplant cholangiopathy.
引用
收藏
页码:1405 / 1413
页数:9
相关论文
共 50 条
  • [41] Bile Composition and Biliary Tract Regeneration During Normothermic Machine Perfusion: Can We Save More Livers?
    Nasralla, David
    De Martin, Eleonora
    TRANSPLANTATION, 2023, 107 (06) : E159 - E160
  • [42] Rouleaux Formation in Human Livers During Normothermic Machine Perfusion
    Harris, M.
    Raigani, S.
    Albert, C.
    Reschke, M.
    Carroll, C.
    Langford, J. T.
    Edwards, C.
    Mulligan, D.
    Haakinson, D.
    Uygun, K.
    Yeh, H.
    Tietjen, G.
    AMERICAN JOURNAL OF TRANSPLANTATION, 2020, 20 : 729 - 730
  • [43] Production of physiological amounts of hemostatic proteins by human donor livers during ex situ long-term normothermic machine perfusion for up to 7 days
    Lascaris, Bianca
    Bodewes, Silke B.
    Adelmeijer, Jelle
    Nijsten, Maarten W. N.
    Porte, Robert J.
    de Meijer, Vincent E.
    Lisman, Ton
    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2024, 22 (11) : 3097 - 3106
  • [44] Ex-Situ Reperfusion Injury/Inflammation: Immuno-Molecular Profiling of Human Livers During Normothermic Machine Perfusion
    Dengu, F.
    Critchley, W.
    Abbas, H.
    Ceresa, C.
    Lo Faro, M.
    Stone, J.
    Aswani, A.
    Coussios, C.
    Ploeg, R.
    Nasralla, D.
    Fildes, J.
    Friend, P.
    AMERICAN JOURNAL OF TRANSPLANTATION, 2023, 23 (06) : S1085 - S1085
  • [45] Biliary Viability Assessment and Treatment Options of Biliary Injury During Normothermic Liver Perfusion-A Systematic Review
    Dingfelder, Jule
    Rauter, Laurin
    Berlakovich, Gabriela A.
    Kollmann, Dagmar
    TRANSPLANT INTERNATIONAL, 2022, 35
  • [46] Rouleaux formation in human livers during normothermic machine perfusion increases vascular resistance and impedes viability
    Harris, M.
    Raigani, S.
    Claire, A.
    Reschke, M.
    Carroll, C.
    Langford, J.
    Edwards, C.
    Haakinson, D.
    Uygun, K.
    Yeh, H.
    Tietjen, G.
    TRANSPLANTATION, 2021, 105 (08) : 75 - 76
  • [47] Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers
    Lau, Ngee-Soon
    Ly, Mark
    Dennis, Claude
    Toomath, Shamus
    Huang, Joanna Lou
    Huang, Joanna
    Ly, Hayden
    Chanda, Sumon
    Marinelli, Tina
    Davis, Rebecca
    Liu, Ken
    McCaughan, Geoff
    Crawford, Michael
    Pulitano, Carlo
    TRANSPLANTATION, 2024, 108 (01) : 198 - 203
  • [48] Normothermic machine perfusion of donor livers without the need for human blood products
    Matton, Alix P. M.
    Burlage, Laura C.
    van Rijn, Rianne
    de Vries, Yvonne
    Karangwa, Shanice A.
    Nijsten, Maarten W.
    Gouw, Annette S. H.
    Wiersema-Buist, Janneke
    Adelmeijer, Jelle
    Westerkamp, Andrie C.
    Lisman, Ton
    Porte, Robert J.
    LIVER TRANSPLANTATION, 2018, 24 (04) : 528 - 538
  • [49] The application of normothermic machine perfusion to bench-test human donor livers
    Reiling, J.
    Simpson, A.
    Bridle, K. R.
    Lockwood, D.
    Santrampurwala, N.
    Britton, L.
    Dejong, C. H. C.
    Crawford, D. H. G.
    Fawcett, J.
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2016, 31 : 115 - 116
  • [50] Metabolic Profiling of Steatotic Human Livers during Ex-Vivo Normothermic Machine Perfusion.
    Raigani, S.
    Karimian, N.
    Huang, V.
    Geerts, S.
    Nagpal, S.
    Uygun, K.
    Yarmush, M.
    Yeh, H.
    AMERICAN JOURNAL OF TRANSPLANTATION, 2019, 19 : 746 - 746