Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

Brüggenwirth, Isabel M A; Porte, Robert J.; Martins, Paulo N.

doi:10.1002/lt.25771

Cited by 38 publications

(44 citation statements)

References 60 publications

(108 reference statements)

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“…In the CCA research process, the EVs in the culture media of CCA were separated mainly by ultracentrifugation [ 61 , 64 , 65 ]. Similarly, EVs are extracted from the serum by ultracentrifugation, and polymer-based precipitation kit [ 95 , 96 ]. However, there is a study that supports some commercial kits, such as ExoQuick and miR-CURY, as being better than ultracentrifugation, even with a limited quantity of EVs [ 92 ].…”

Section: Evs As Novel Biomarkers For Ccamentioning

confidence: 99%

“…However, there is a study that supports some commercial kits, such as ExoQuick and miR-CURY, as being better than ultracentrifugation, even with a limited quantity of EVs [ 92 ]. Bile is a lipid-rich fluid, that is secreted primarily by hepatocytes, and contains almost all body components: lipids, proteins, carbohydrates, vitamins, mineral salts and trace elements [ 96 , 97 ]. Because of the characteristics and complexity of bile extraction, we mainly summarize the isolation of bile here.…”

Section: Evs As Novel Biomarkers For Ccamentioning

confidence: 99%

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The role of extracellular vesicles in cholangiocarcinoma

Bai

et al. 2020

Cancer Cell Int

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Cholangiocarcinoma (CCA) is a rare tumor that arises from cholangiocytes, the epithelial cells of the bile duct. The tumor is characterized by insidious onset, high degree of malignancy, poor prognosis and high recurrence rate. Due to the lack of specific biomarkers, it is difficult to diagnose CCA early and evaluate prognosis. Extracellular vesicles (EVs), which include apoptotic bodies, microvesicles and exosomes, have emerged as having important roles in cellto-cell communication in both normal physiology and pathological conditions. Some research has found that EVs play a crucial role in the occurrence and development of CCA. EVs can carry specific molecular substances such as nucleic acids and proteins, which have potential for the diagnosis and therapy of CCA. This article reviews the current knowledge on the role of EVs in CCA. We highlight EVs and their functions in the physiology and pathophysiology of CCA, and discuss their therapeutic potential and their role as biomarkers.

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Section: Evs As Novel Biomarkers For Ccamentioning

confidence: 99%

Section: Evs As Novel Biomarkers For Ccamentioning

confidence: 99%

The role of extracellular vesicles in cholangiocarcinoma

Bai

et al. 2020

Cancer Cell Int

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“…Alternatively, perfusion at an intermediate temperature range (22)(23)(24)(25)(26)(27)(28)(29)(30) • C), termed subnormothermic machine perfusion (SNMP), has some potential advantages that warrant further exploration (3). At intermediate temperatures, the oxygen requirement of the graft is low enough to be met with a simple acellular perfusate, yet the metabolic activity of the graft is sufficiently high to support the production of bile, which is emerging as an important indicator of graft injury and viability (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model

et al. 2022

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BackgroundSubnormothermic machine perfusion (SNMP) of liver grafts is currently less clinically developed than normothermic and hypothermic approaches, but may have logistical advantages. At intermediate temperatures, the oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, however, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability. In this study, we hypothesized that the biliary compartment would be more sensitive than perfusate in detecting graft injury during SNMP.MethodsTo test this hypothesis in a rat model, we performed liver transplants with DCD and control liver grafts after 1 h of acellular room temperature machine perfusion (acRTMP) or static cold storage (SCS). Point of care liver function tests were measured in biliary and perfusate samples after 1 h of machine perfusion. Following transplantation, rats were sacrificed at 24 h for assessment of post-transplant graft function and histology.ResultsAll point-of-care liver function tests were significantly more concentrated in the biliary compartment than the perfusate compartment during acRTMP. DCD liver grafts could be distinguished from control liver grafts by significantly higher markers of hepatocyte injury (AST, ALT) in the biliary compartment, but not in the perfusate compartment. Classical markers of cholangiocyte injury, such as gammy-glut amyl transferase (GGT), amylase (AML), and alkaline phosphatase were detectable in the biliary compartment, but not in the perfusate compartment. In comparison to SCS, graft preservation by acRTMP produced a significant survival benefit in DCD liver transplantation (75 vs. 0%, p < 0.0030).ConclusionTogether, these findings demonstrate that during acRTMP, the biliary compartment may be a more sensitive indicator of graft injury than the perfusate compartment. Moreover, acRTMP provides superior graft preservation to SCS in rat DCD liver transplantation.

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“…Previous studies have shown that livers meeting hepatocellular viability criteria still developed biliary complications after transplantation 9,12 . Therefore, bile composition may be considered an additional parameter of bile duct viability 14 . This is underlined by a study showing low hepatocellular injury during NMP of discarded human livers but high bile duct injury on histology 15 .…”

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confidence: 99%