{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:04:43Z","timestamp":1781183083954,"version":"3.54.1"},"reference-count":110,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Ministerstwo Edukacji i Nauki","doi-asserted-by":"publisher","award":["NdS\u2010II\/SP\/0602\/2023\/01"],"award-info":[{"award-number":["NdS\u2010II\/SP\/0602\/2023\/01"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The goal of achieving clinical operational tolerance in liver transplantation has sparked significant interest, driven by the desire to mitigate the long\u2010term adverse effects of immunosuppression. Advances in understanding the immunological mechanisms underpinning operational tolerance in liver transplantation have highlighted the central role of regulatory T cells and tolerogenic dendritic cells. These cells actively suppress effector immune responses and aid in achieving operational tolerance. Immunosuppressive medication differentially influences the expansion, survival, and function of these cells, demonstrating the importance of understanding the potential of immunosuppressive regimens to optimize the possibility of achieving an immunosuppression\u2010free state. The potential of stepwise immunosuppressive reduction to achieve operational tolerance without compromising graft function has been demonstrated. The immunosuppressive withdrawal protocols underline the feasibility and safety of immunosuppressive withdrawal in selected liver transplant recipients, highlighting factors such as time since transplantation, recipient age, and gender as strong predictors of success. Furthermore, minimization of immunosuppressive, even early post transplantation, has been shown to be successful and sets the stage for successful immunosuppression withdrawal later. This review highlights the necessity to optimize immunosuppressive regimens by demonstrating its possibility to aid in achieving minimal immunosuppressive to maximize success rates of drug withdrawal and diminish the cumulative immunosuppressive related complications to increase the quality of life of liver transplant recipients.<\/jats:p>","DOI":"10.1111\/liv.70659","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T02:44:19Z","timestamp":1778035459000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Induction of Clinical Operational Tolerance Through Immunosuppression Minimization: Less Is More?"],"prefix":"10.1111","volume":"46","author":[{"given":"Emilia","family":"Knio\u0142a","sequence":"first","affiliation":[{"name":"Department of Transplantology, Immunology, Nephrology and Internal Medicine Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Foroncewicz","sequence":"additional","affiliation":[{"name":"Department of Transplantology, Immunology, Nephrology and Internal Medicine Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lerut","sequence":"additional","affiliation":[{"name":"IREC Institute for Experimental and Clinical Research (IREC) Universit\u00e9 Catholique Louvain (UCL)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leszek","family":"P\u0105czek","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Medical University of Warsaw  Warsaw Poland"},{"name":"Institute of Biochemistry and Biophysics Polish Academy of Sciences  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6613-7638","authenticated-orcid":false,"given":"Krzysztof","family":"Mucha","sequence":"additional","affiliation":[{"name":"Department of Transplantology, Immunology, Nephrology and Internal Medicine Medical University of Warsaw  Warsaw Poland"},{"name":"Institute of Biochemistry and Biophysics Polish Academy of Sciences  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"e_1_2_14_2_1","article-title":"Thomas Earl Starzl, MD, PhD (1926\u20132017): Father of Transplantation","volume":"8","author":"Eghtesad B.","year":"2017","journal-title":"International Journal of Organ Transplantation Medicine"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.23481"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13909"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-007-0001-7"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26426"},{"key":"e_1_2_14_7_1","first-page":"283","article-title":"Complete Immunosuppression Withdrawal and Subsequent Allograft Function Among Pediatric Recipients of Parental Living Donor Liver Transplants","volume":"307","author":"Feng S.","year":"2012","journal-title":"Journal of the American Medical Association"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.04.003"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2022.06.007"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2023.06.007"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002650"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.21903"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i35.5356"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2019.05.008"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021744"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.21126"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-023-08065-2"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13255"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.15226\/2372-0948\/3\/4\/00136"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-024-10703-4"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-024-10766-3"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00184"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.01.030"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2343"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.585819"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.7.4752"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.08.014"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.5916"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.04.010"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00179"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh207"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01514"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2024.09.009"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82771"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.126194"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28459"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04269.x"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14029"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2009.08.043"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.4067\/S0716-97602010000300010"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182590d8f"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2005.01.006"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2020.152031"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2008.12.008"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2004.00672.x"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001379"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan3085"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp586"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2008.01090.x"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.07.014"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxq001"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2012.09.091"},{"issue":"1","key":"e_1_2_14_53_1","article-title":"Induction Immunosuppression in Adults Undergoing Liver Transplantation: A Network Meta\u2010Analysis","volume":"1","author":"Best L. M. J.","year":"2020","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_14_54_1","first-page":"361","article-title":"Rabbit Anti\u2010Thymocyte Globulin but Not Horse Anti\u2010Thymocyte Globulin Promotes Expansion of Functional CD4+CD25highFOXP3+ Regulatory T Cells in Vitro","volume":"180","author":"Feng X.","year":"2008","journal-title":"Journal of Immunology"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03978.x"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-214437"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12030382"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-13-70"},{"key":"e_1_2_14_59_1","first-page":"384","article-title":"Immunoregulatory Effects of Rabbit Anti\u2010Thymocyte Globulin on Human T Cells and Monocytes in Vitro","volume":"151","author":"Buszko M.","year":"2017","journal-title":"Immunology"},{"key":"e_1_2_14_60_1","first-page":"6422","article-title":"Comparative Study of Human and Cynomolgus T\u2010Cell Depletion With Rabbit Anti\u2010Thymocyte Globulin Treatment: Dose Adjustment in a Non\u2010Human Primate Kidney Transplantation Model","volume":"11","author":"Kwon Y.","year":"2019","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxac105"},{"key":"e_1_2_14_62_1","first-page":"2345","article-title":"Effect of Daclizumab on Regulatory T Cells in Humans","volume":"123","author":"Hartemann A.","year":"2013","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_14_63_1","article-title":"Impact of Basiliximab on Regulatory T Cells and Clinical Outcomes in Pediatric Liver Transplantation","volume":"12","author":"L\u00f3pez\u2010Abente J.","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2007.01842.x"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620835114"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01396.x"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(02)02980-9"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31520"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2009.50.6.784"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15205"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000162084.46555.10"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000058472.71775.7D"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2004.00743.x"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000266678.32250.76"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.23686"},{"key":"e_1_2_14_76_1","unstructured":"E.Knio\u0142a B.Foroncewicz J.Lerut et\u00a0al. The minimization of immunosuppression in liver transplant recipients: a 3\u2010year patient follow\u2010up. E\u2010poster presented at: ESOT Congress 2023."},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199501270-00010"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199701270-00012"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270406"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182003db7"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.11.047"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.17021"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000005026"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.12.001"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04140.x"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31819009c9"},{"key":"e_1_2_14_87_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002943"},{"key":"e_1_2_14_88_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000000969"},{"key":"e_1_2_14_89_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001006"},{"key":"e_1_2_14_90_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15396"},{"key":"e_1_2_14_91_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15764"},{"key":"e_1_2_14_92_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12206546"},{"key":"e_1_2_14_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2024.12.002"},{"key":"e_1_2_14_94_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979471"},{"key":"e_1_2_14_95_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31816dd64a"},{"key":"e_1_2_14_96_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13617"},{"key":"e_1_2_14_97_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001105"},{"key":"e_1_2_14_98_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15870"},{"key":"e_1_2_14_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13175-3"},{"key":"e_1_2_14_100_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15592"},{"key":"e_1_2_14_101_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02401"},{"key":"e_1_2_14_102_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01203"},{"key":"e_1_2_14_103_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02525"},{"key":"e_1_2_14_104_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-019-00684-7"},{"key":"e_1_2_14_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.75"},{"key":"e_1_2_14_106_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31818febc4"},{"key":"e_1_2_14_107_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e318188d3e6"},{"key":"e_1_2_14_108_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31036"},{"key":"e_1_2_14_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2005.03.141"},{"key":"e_1_2_14_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2022.04.023"},{"key":"e_1_2_14_111_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28681"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70659","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.70659","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T12:56:02Z","timestamp":1781182562000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":110,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/liv.70659"],"URL":"https:\/\/doi.org\/10.1111\/liv.70659","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]},"assertion":[{"value":"2025-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70659"}}