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  1. Article ; Online: Salvage of a Right-extended Split Liver Graft Using Ex Situ Normothermic Machine Perfusion-A New Therapeutic Horizon.

    Kathirvel, Manikandan / Nasralla, David / Iype, Satheesh / Tzerbinis, Helen / Crick, Keziah / Cortes Cerisuelo, Miriam / Pollok, Joerg-Matthias

    Transplantation

    2022  Volume 106, Issue 6, Page(s) e320–e321

    MeSH term(s) Liver/surgery ; Liver Transplantation/adverse effects ; Organ Preservation ; Perfusion
    Language English
    Publishing date 2022-05-23
    Publishing country United States
    Document type Letter
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000004067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Observations on the ex situ perfusion of livers for transplantation.

    Watson, Christopher J E / Kosmoliaptsis, Vasilis / Pley, Caitlin / Randle, Lucy / Fear, Corinna / Crick, Keziah / Gimson, Alexander E / Allison, Michael / Upponi, Sara / Brais, Rebecca / Jochmans, Ina / Butler, Andrew J

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2018  Volume 18, Issue 8, Page(s) 2005–2020

    Abstract: Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the ... ...

    Abstract Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with posttransplant peak transaminase levels. Lactate clearance occurred within 3 hours in 46 of 47 perfusions, and glucose rose initially during perfusion in 44. Three livers required higher levels of bicarbonate support to maintain physiological pH, including one developing primary nonfunction. Bile production did not correlate with viability or cholangiopathy, but bile pH, measured in 16 of the 22 transplanted livers, identified three livers that developed cholangiopathy (peak pH < 7.4) from those that did not (pH > 7.5). In the 11 research livers where it could be studied, bile pH > 7.5 discriminated between the 6 livers exhibiting >50% circumferential stromal necrosis of septal bile ducts and 4 without necrosis; one liver with 25-50% necrosis had a maximum pH 7.46. Liver viability during normothermic perfusion can be assessed using a combination of transaminase release, glucose metabolism, lactate clearance, and maintenance of acid-base balance. Evaluation of bile pH may offer a valuable insight into bile duct integrity and risk of posttransplant ischemic cholangiopathy.
    MeSH term(s) Adult ; Bile Ducts/metabolism ; Biomarkers/metabolism ; Female ; Follow-Up Studies ; Hepatocytes/metabolism ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Organ Preservation/methods ; Perfusion/methods ; Primary Graft Dysfunction/prevention & control ; Prognosis ; Reperfusion Injury/prevention & control ; Tissue Donors/supply & distribution ; Tissue and Organ Procurement/standards ; Young Adult
    Chemical Substances Biomarkers
    Language English
    Publishing date 2018-03-14
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.14687
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival.

    Watson, Christopher J E / Hunt, Fiona / Messer, Simon / Currie, Ian / Large, Stephen / Sutherland, Andrew / Crick, Keziah / Wigmore, Stephen J / Fear, Corrina / Cornateanu, Sorina / Randle, Lucy V / Terrace, John D / Upponi, Sara / Taylor, Rhiannon / Allen, Elisa / Butler, Andrew J / Oniscu, Gabriel C

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2019  Volume 19, Issue 6, Page(s) 1745–1758

    Abstract: Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after ...

    Abstract Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors. NRP was performed on 70 DCD donors from whom 43 livers were transplanted. These were compared with 187 non-NRP DCD donor livers transplanted at the same two UK centers in the same period. The use of NRP was associated with a reduction in early allograft dysfunction (12% for NRP vs. 32% for non-NRP livers, P = .0076), 30-day graft loss (2% NRP livers vs. 12% non-NRP livers, P = .0559), freedom from ischemic cholangiopathy (0% vs. 27% for non-NRP livers, P < .0001), and fewer anastomotic strictures (7% vs. 27% non-NRP, P = .0041). After adjusting for other factors in a multivariable analysis, NRP remained significantly associated with freedom from ischemic cholangiopathy (P < .0001). These data suggest that NRP during organ recovery from DCD donors leads to superior liver outcomes compared to conventional organ recovery.
    MeSH term(s) Adolescent ; Adult ; Aged ; Bile Duct Diseases/prevention & control ; Bile Ducts/blood supply ; Child ; Death ; Delayed Graft Function/prevention & control ; Extracorporeal Circulation ; Female ; Graft Survival ; Humans ; Ischemia/prevention & control ; Liver Transplantation/adverse effects ; Liver Transplantation/methods ; Male ; Middle Aged ; Organ Preservation/adverse effects ; Organ Preservation/methods ; Perfusion/methods ; Retrospective Studies ; Temperature ; Tissue and Organ Harvesting/adverse effects ; Tissue and Organ Harvesting/methods ; Tissue and Organ Procurement/methods ; Young Adult
    Language English
    Publishing date 2019-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.15241
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Transient Cold Storage Prior to Normothermic Liver Perfusion May Facilitate Adoption of a Novel Technology.

    Ceresa, Carlo D L / Nasralla, David / Watson, Christopher J E / Butler, Andrew J / Coussios, Constantin C / Crick, Keziah / Hodson, Leanne / Imber, Charles / Jassem, Wayel / Knight, Simon R / Mergental, Hynek / Ploeg, Rutger J / Pollok, Joerg M / Quaglia, Alberto / Shapiro, A M James / Weissenbacher, Annemarie / Friend, Peter J

    Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

    2019  Volume 25, Issue 10, Page(s) 1503–1513

    Abstract: Clinical adoption of normothermic machine perfusion (NMP) may be facilitated by simplifying logistics and reducing costs. This can be achieved by cold storage of livers for transportation to recipient centers before commencing NMP. The purpose of this ... ...

    Abstract Clinical adoption of normothermic machine perfusion (NMP) may be facilitated by simplifying logistics and reducing costs. This can be achieved by cold storage of livers for transportation to recipient centers before commencing NMP. The purpose of this study was to assess the safety and feasibility of post-static cold storage normothermic machine perfusion (pSCS-NMP) in liver transplantation. In this multicenter prospective study, 31 livers were transplanted. The primary endpoint was 30-day graft survival. Secondary endpoints included the following: peak posttransplant aspartate aminotransferase (AST), early allograft dysfunction (EAD), postreperfusion syndrome (PRS), adverse events, critical care and hospital stay, biliary complications, and 12-month graft survival. The 30-day graft survival rate was 94%. Livers were preserved for a total of 14 hours 10 minutes ± 4 hours 46 minutes, which included 6 hours 1 minute ± 1 hour 19 minutes of static cold storage before 8 hours 24 minutes ± 4 hours 4 minutes of NMP. Median peak serum AST in the first 7 days postoperatively was 457 U/L (92-8669 U/L), and 4 (13%) patients developed EAD. PRS was observed in 3 (10%) livers. The median duration of initial critical care stay was 3 days (1-20 days), and median hospital stay was 13 days (7-31 days). There were 7 (23%) patients who developed complications of grade 3b severity or above, and 2 (6%) patients developed biliary complications: 1 bile leak and 1 anastomotic stricture with no cases of ischemic cholangiopathy. The 12-month overall graft survival rate (including death with a functioning graft) was 84%. In conclusion, this study demonstrates that pSCS-NMP was feasible and safe, which may facilitate clinical adoption.
    MeSH term(s) Adolescent ; Adult ; Aged ; Allografts/blood supply ; Cold Temperature ; End Stage Liver Disease/diagnosis ; End Stage Liver Disease/surgery ; Feasibility Studies ; Female ; Follow-Up Studies ; Graft Survival ; Humans ; Intensive Care Units/statistics & numerical data ; Length of Stay/statistics & numerical data ; Liver/blood supply ; Liver Transplantation/adverse effects ; Liver Transplantation/methods ; Male ; Middle Aged ; Organ Preservation/adverse effects ; Organ Preservation/methods ; Perfusion/adverse effects ; Perfusion/methods ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Prospective Studies ; Severity of Illness Index ; Time Factors ; Warm Ischemia/adverse effects ; Young Adult
    Language English
    Publishing date 2019-07-18
    Publishing country United States
    Document type Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2006866-9
    ISSN 1527-6473 ; 1527-6465
    ISSN (online) 1527-6473
    ISSN 1527-6465
    DOI 10.1002/lt.25584
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.

    Sampaziotis, Fotios / Muraro, Daniele / Tysoe, Olivia C / Sawiak, Stephen / Beach, Timothy E / Godfrey, Edmund M / Upponi, Sara S / Brevini, Teresa / Wesley, Brandon T / Garcia-Bernardo, Jose / Mahbubani, Krishnaa / Canu, Giovanni / Gieseck, Richard / Berntsen, Natalie L / Mulcahy, Victoria L / Crick, Keziah / Fear, Corrina / Robinson, Sharayne / Swift, Lisa /
    Gambardella, Laure / Bargehr, Johannes / Ortmann, Daniel / Brown, Stephanie E / Osnato, Anna / Murphy, Michael P / Corbett, Gareth / Gelson, William T H / Mells, George F / Humphreys, Peter / Davies, Susan E / Amin, Irum / Gibbs, Paul / Sinha, Sanjay / Teichmann, Sarah A / Butler, Andrew J / See, Teik Choon / Melum, Espen / Watson, Christopher J E / Saeb-Parsy, Kourosh / Vallier, Ludovic

    Science (New York, N.Y.)

    2021  Volume 371, Issue 6531, Page(s) 839–846

    Abstract: Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. ... ...

    Abstract Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture. However, cholangiocyte organoids remain plastic and resume their in vivo signatures when transplanted back in the biliary tree. We then utilize a model of cell engraftment in human livers undergoing ex vivo normothermic perfusion to demonstrate that this property allows extrahepatic organoids to repair human intrahepatic ducts after transplantation. Our results provide proof of principle that cholangiocyte organoids can be used to repair human biliary epithelium.
    MeSH term(s) Animals ; Bile ; Bile Duct Diseases/therapy ; Bile Ducts/cytology ; Bile Ducts/physiology ; Bile Ducts, Intrahepatic/cytology ; Bile Ducts, Intrahepatic/physiology ; Cell- and Tissue-Based Therapy ; Common Bile Duct/cytology ; Epithelial Cells/cytology ; Epithelial Cells/physiology ; Gallbladder/cytology ; Gene Expression Regulation ; Humans ; Liver/physiology ; Liver Transplantation ; Mesenchymal Stem Cell Transplantation ; Mice ; Organoids/physiology ; Organoids/transplantation ; RNA-Seq ; Tissue and Organ Procurement ; Transcriptome
    Language English
    Publishing date 2021-03-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aaz6964
    Database MEDical Literature Analysis and Retrieval System OnLINE

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