Isabella Lurje, Paul Horn, Adrien Guillot, Deniz Uluk, Frederik Schliephake, Luna Rohm, Dina Katharina Liefke-Biegel, Malte Lehnert, Katharina Remih, Rabea Hokamp, Wiebke Werner, Alix Bruneau, Justus Pein, Yaroslava Shevchenko, Ingrid Wei Zhang, Pavitra Kumar, Cornelius Engelmann, Moritz Peiseler, Janina Eden, Philipp Dutkowski, David Meierhofer, Nadine Gaisa, Pavel Strnad, Johann Pratschke, Linda Hammerich, Frank Tacke, Georg Lurje
{"title":"低温充氧和常温机器灌注可减轻肝移植术后先天性全身和肝脏炎症。","authors":"Isabella Lurje, Paul Horn, Adrien Guillot, Deniz Uluk, Frederik Schliephake, Luna Rohm, Dina Katharina Liefke-Biegel, Malte Lehnert, Katharina Remih, Rabea Hokamp, Wiebke Werner, Alix Bruneau, Justus Pein, Yaroslava Shevchenko, Ingrid Wei Zhang, Pavitra Kumar, Cornelius Engelmann, Moritz Peiseler, Janina Eden, Philipp Dutkowski, David Meierhofer, Nadine Gaisa, Pavel Strnad, Johann Pratschke, Linda Hammerich, Frank Tacke, Georg Lurje","doi":"10.1136/gutjnl-2026-338907","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immune-mediated injury drives ischaemia-reperfusion injury (IRI) following liver transplantation. While hypothermic oxygenated (HOPE) and normothermic machine perfusion (NMP) improve clinical outcomes, their immunological effects in humans remain unclear.</p><p><strong>Objective: </strong>To examine hepatic and systemic immune responses across preservation strategies in a randomised controlled clinical setting.</p><p><strong>Design: </strong>In this mechanistic substudy of the HOPE-NMP randomised controlled trial (NCT04644744), we analysed immune responses in n=47 recipients of extended criteria donor livers from brain-dead donors randomised to static cold storage (SCS), end-ischaemic HOPE or end-ischaemic NMP. Liver biopsies were obtained at organ arrival and early IRI. Blood samples were collected preoperatively, during reperfusion and on postoperative days 1, 2, 3 and 7.</p><p><strong>Methods: </strong>Analyses included spectral flow cytometry, multiplex immunofluorescence with spatial analyses, cytokine profiling, cellular bioenergetics and mass spectrometry.</p><p><strong>Results: </strong>In human liver allografts, both HOPE and NMP reduced neutrophil infiltration during early IRI, without altering intrahepatic spatial distribution. Machine perfusion induced phenotypic modulation of graft-infiltrating myeloid cells, characterised by downregulation of pro-inflammatory and adhesion markers. Peripheral lymphocyte numbers, particularly of NK cells and T cells, normalised faster after HOPE, compared with SCS and NMP groups, correlating with reduced liver injury. Absolute and relative systemic neutrophil numbers were lower in HOPE-recipients. Machine perfusion decreased the inflammatory activation of circulating myeloid and innate lymphoid cells, while inhibitory immune checkpoints were upregulated postoperatively.</p><p><strong>Conclusions: </strong>In a randomised controlled trial using human samples, HOPE and NMP differentially modulate hepatic and systemic immune responses, attenuating neutrophil-driven inflammation and promoting immune regulation after liver transplantation.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6000,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hypothermic oxygenated and normothermic machine perfusion mitigate innate systemic and hepatic inflammation after liver transplantation.\",\"authors\":\"Isabella Lurje, Paul Horn, Adrien Guillot, Deniz Uluk, Frederik Schliephake, Luna Rohm, Dina Katharina Liefke-Biegel, Malte Lehnert, Katharina Remih, Rabea Hokamp, Wiebke Werner, Alix Bruneau, Justus Pein, Yaroslava Shevchenko, Ingrid Wei Zhang, Pavitra Kumar, Cornelius Engelmann, Moritz Peiseler, Janina Eden, Philipp Dutkowski, David Meierhofer, Nadine Gaisa, Pavel Strnad, Johann Pratschke, Linda Hammerich, Frank Tacke, Georg Lurje\",\"doi\":\"10.1136/gutjnl-2026-338907\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immune-mediated injury drives ischaemia-reperfusion injury (IRI) following liver transplantation. While hypothermic oxygenated (HOPE) and normothermic machine perfusion (NMP) improve clinical outcomes, their immunological effects in humans remain unclear.</p><p><strong>Objective: </strong>To examine hepatic and systemic immune responses across preservation strategies in a randomised controlled clinical setting.</p><p><strong>Design: </strong>In this mechanistic substudy of the HOPE-NMP randomised controlled trial (NCT04644744), we analysed immune responses in n=47 recipients of extended criteria donor livers from brain-dead donors randomised to static cold storage (SCS), end-ischaemic HOPE or end-ischaemic NMP. Liver biopsies were obtained at organ arrival and early IRI. Blood samples were collected preoperatively, during reperfusion and on postoperative days 1, 2, 3 and 7.</p><p><strong>Methods: </strong>Analyses included spectral flow cytometry, multiplex immunofluorescence with spatial analyses, cytokine profiling, cellular bioenergetics and mass spectrometry.</p><p><strong>Results: </strong>In human liver allografts, both HOPE and NMP reduced neutrophil infiltration during early IRI, without altering intrahepatic spatial distribution. Machine perfusion induced phenotypic modulation of graft-infiltrating myeloid cells, characterised by downregulation of pro-inflammatory and adhesion markers. Peripheral lymphocyte numbers, particularly of NK cells and T cells, normalised faster after HOPE, compared with SCS and NMP groups, correlating with reduced liver injury. Absolute and relative systemic neutrophil numbers were lower in HOPE-recipients. Machine perfusion decreased the inflammatory activation of circulating myeloid and innate lymphoid cells, while inhibitory immune checkpoints were upregulated postoperatively.</p><p><strong>Conclusions: </strong>In a randomised controlled trial using human samples, HOPE and NMP differentially modulate hepatic and systemic immune responses, attenuating neutrophil-driven inflammation and promoting immune regulation after liver transplantation.</p>\",\"PeriodicalId\":12825,\"journal\":{\"name\":\"Gut\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":24.6000,\"publicationDate\":\"2026-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gut\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/gutjnl-2026-338907\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/gutjnl-2026-338907","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Hypothermic oxygenated and normothermic machine perfusion mitigate innate systemic and hepatic inflammation after liver transplantation.
Background: Immune-mediated injury drives ischaemia-reperfusion injury (IRI) following liver transplantation. While hypothermic oxygenated (HOPE) and normothermic machine perfusion (NMP) improve clinical outcomes, their immunological effects in humans remain unclear.
Objective: To examine hepatic and systemic immune responses across preservation strategies in a randomised controlled clinical setting.
Design: In this mechanistic substudy of the HOPE-NMP randomised controlled trial (NCT04644744), we analysed immune responses in n=47 recipients of extended criteria donor livers from brain-dead donors randomised to static cold storage (SCS), end-ischaemic HOPE or end-ischaemic NMP. Liver biopsies were obtained at organ arrival and early IRI. Blood samples were collected preoperatively, during reperfusion and on postoperative days 1, 2, 3 and 7.
Methods: Analyses included spectral flow cytometry, multiplex immunofluorescence with spatial analyses, cytokine profiling, cellular bioenergetics and mass spectrometry.
Results: In human liver allografts, both HOPE and NMP reduced neutrophil infiltration during early IRI, without altering intrahepatic spatial distribution. Machine perfusion induced phenotypic modulation of graft-infiltrating myeloid cells, characterised by downregulation of pro-inflammatory and adhesion markers. Peripheral lymphocyte numbers, particularly of NK cells and T cells, normalised faster after HOPE, compared with SCS and NMP groups, correlating with reduced liver injury. Absolute and relative systemic neutrophil numbers were lower in HOPE-recipients. Machine perfusion decreased the inflammatory activation of circulating myeloid and innate lymphoid cells, while inhibitory immune checkpoints were upregulated postoperatively.
Conclusions: In a randomised controlled trial using human samples, HOPE and NMP differentially modulate hepatic and systemic immune responses, attenuating neutrophil-driven inflammation and promoting immune regulation after liver transplantation.
期刊介绍：
Gut is a renowned international journal specializing in gastroenterology and hepatology, known for its high-quality clinical research covering the alimentary tract, liver, biliary tree, and pancreas. It offers authoritative and current coverage across all aspects of gastroenterology and hepatology, featuring articles on emerging disease mechanisms and innovative diagnostic and therapeutic approaches authored by leading experts.
As the flagship journal of BMJ's gastroenterology portfolio, Gut is accompanied by two companion journals: Frontline Gastroenterology, focusing on education and practice-oriented papers, and BMJ Open Gastroenterology for open access original research.
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