{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:35:30Z","timestamp":1790116530794,"version":"4.0.1"},"reference-count":28,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Neovii Biotech GmbH, Gr\u00e4felfing, Germany"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Induction therapy with depleting antibodies in the setting of liver transplantation (LT) is discussed controversially to this day. The rabbit antithymocyteglobulin (ATG) Thymoglobulin (rATG) was introduced as early as 1984 and was frequently used as a standard regime for induction therapy after LT. There are no public reports characterizing Grafalon (ATG-F), a novel ATG, as an induction agent after LT. Objectives: The aim of this observational non-interventional study was to investigate the safety and efficacy of Grafalon induction therapy and characterize its clinical effects in the setting of LT. Methods: A cohort of 80 patients undergoing deceased donor LT at the Medical University of Vienna and receiving Grafalon as part of the clinical standard immunosuppressive regimen was prospectively included between March 2021 and November 2022. Patients were monitored closely for leukocytopenia and thrombocytopenia during the first postoperative week and followed up for incidence and severity of biopsy-proven acute rejection (BPAR), overall survival, and bacterial infections in the first year after LT. Results: The incidences of thrombocytopenia and leukocytopenia following Grafalon treatment peaked on postoperative day four, with 64% and 31%, respectively. However, there were no cases of severe leukocytopenia after the first postoperative week. Induction therapy with Grafalon resulted in a rate of localized bacterial infections and bacteremia of 28% and 21%, respectively. The rate of BPAR was 12.5% in the first year after LT; the one-year survival rate in this cohort was 90%. Conclusions: Overall, this study provides evidence of the safety and efficacy of Grafalon as an induction agent. Further studies investigating the potential long-term effects of Grafalon, as well as comparison studies with different immunosuppressive regimens, are needed in order to draw further conclusions.<\/jats:p>","DOI":"10.3390\/jcm13144051","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T11:33:22Z","timestamp":1720697602000},"page":"4051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunosuppressive Induction Therapy Using the Antithymocyteglobulin Grafalon: A Single-Center Non-Interventional Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Nikolaus","family":"Becker","sequence":"first","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-9163","authenticated-orcid":false,"given":"David","family":"Pereyra","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"},{"name":"Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jule","family":"Dingfelder","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"},{"name":"Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Tortopis","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Saffarian Zadeh","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moriz","family":"Riha","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sertac","family":"Kacar","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6871-9343","authenticated-orcid":false,"given":"Thomas","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-7874","authenticated-orcid":false,"given":"Gabriela A.","family":"Berlakovich","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0863-2876","authenticated-orcid":false,"given":"Georg","family":"Gy\u00f6ri","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Transplantation, Medical University of Vienna, 1090 Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ref_1","first-page":"96","article-title":"Update on Immunosuppression in Liver Transplantation","volume":"9","author":"Tasdogan","year":"2019","journal-title":"Euroasian J. Hepatogastroenterol."},{"key":"ref_2","unstructured":"Dababneh, Y., and Mousa, O.Y. (2024). Liver Transplantation. StatPearls, StatPearls Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1097\/TP.0000000000002147","article-title":"International Liver Transplantation Society Consensus Statement on Immunosuppression in Liver Transplant Recipients","volume":"102","author":"Charlton","year":"2018","journal-title":"Transplantation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.3748\/wjg.v22.i10.2922","article-title":"Advances in Liver Transplantation Allocation Systems","volume":"22","author":"Schilsky","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.jceh.2023.04.005","article-title":"Liver Transplantation: Contraindication and Ineligibility","volume":"13","author":"Puri","year":"2023","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1097\/MOT.0000000000000397","article-title":"Liver Allocation and Distribution: Time for a Change","volume":"22","author":"Deshpande","year":"2017","journal-title":"Curr. Opin. Organ. Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1001\/jamasurg.2021.6781","article-title":"Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant","volume":"157","author":"Markmann","year":"2022","journal-title":"JAMA Surg."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Panconesi, R., Flores Carvalho, M., Mueller, M., Meierhofer, D., Dutkowski, P., Muiesan, P., and Schlegel, A. (2021). Viability Assessment in Liver Transplantation\u2014What Is the Impact of Dynamic Organ Preservation?. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020161"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1097\/SLA.0000000000005110","article-title":"Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-Transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death: Results From a Multicenter Randomized Controlled Trial (HOPE ECD-DBD)","volume":"274","author":"Czigany","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.trre.2012.06.002","article-title":"Review Article: Use of Induction Therapy in Liver Transplantation","volume":"26","author":"Rostaing","year":"2012","journal-title":"Transplant. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1111\/ajt.15513","article-title":"The Use of Induction Therapy in Liver Transplantation Is Highly Variable and Is Associated with Posttransplant Outcomes","volume":"19","author":"Bittermann","year":"2019","journal-title":"Am. J. Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrgastro.2015.172","article-title":"Keys to Long-Term Care of the Liver Transplant Recipient","volume":"12","author":"Watt","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101689","DOI":"10.1016\/j.bpg.2020.101689","article-title":"Post Liver Transplant Recurrent and de Novo Viral Infections","volume":"46","author":"Jothimani","year":"2020","journal-title":"Best. Pract. Res. Clin. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/01.JAA.0000527694.68417.0a","article-title":"A Systems-Based Approach to Patient Care after Liver Transplantation","volume":"31","author":"Gillespie","year":"2018","journal-title":"JAAPA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e15085","DOI":"10.1111\/ctr.15085","article-title":"Evolving Challenges with Long-Term Care of Liver Transplant Recipients","volume":"37","author":"Odenwald","year":"2023","journal-title":"Clin. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/j.jceh.2022.06.007","article-title":"Immunosuppressive Drugs in Liver Transplant: An Insight","volume":"12","author":"Panackel","year":"2022","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/SLA.0000000000002650","article-title":"No Gains in Long-Term Survival After Liver Transplantation Over the Past Three Decades","volume":"269","author":"Rana","year":"2019","journal-title":"Ann. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1007\/s40265-014-0277-6","article-title":"New Directions for Rabbit Antithymocyte Globulin (Thymoglobulin\u00ae) in Solid Organ Transplants, Stem Cell Transplants and Autoimmunity","volume":"74","author":"Mohty","year":"2014","journal-title":"Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1111\/ajt.12514","article-title":"A Comprehensive and Quantitative Analysis of the Major Specificities in Rabbit Antithymocyte Globulin Preparations","volume":"13","author":"Popow","year":"2013","journal-title":"Am. J. Transplant."},{"key":"ref_20","unstructured":"(2024, May 20). Clinical Investigation of Immunosuppressants for Solid Organ Transplantation\u2014Scientific Guideline|European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/clinical-investigation-immunosuppressants-solid-organ-transplantation-scientific-guideline."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee 2 (2023). Diagnosis and Classification of Diabetes: Standards of Care in Diabetes\u20142024. Diabetes Care, 47, S20\u2013S42.","DOI":"10.2337\/dc24-S002"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1111\/ajt.13909","article-title":"2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection","volume":"16","author":"Demetris","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"691","DOI":"10.2165\/11315940-000000000-00000","article-title":"Rabbit Antithymocyte Globulin (Thymoglobulin\u00ae): 25 Years and New Frontiers in Solid Organ Transplantation and Haematology","volume":"70","author":"Gaber","year":"2010","journal-title":"Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1399-0012.2005.00375.x","article-title":"Thymoglobulin Induction Protects Liver Allografts from Ischemia\/Reperfusion Injury","volume":"19","author":"Bogetti","year":"2005","journal-title":"Clin. Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13S","DOI":"10.1016\/S0041-1345(97)80455-1","article-title":"Use of Thymoglobulin Induction Therapy in the Prevention of Acute Graft Rejection Episodes Following Liver Transplantation","volume":"29","author":"Tchervenkov","year":"1997","journal-title":"Transplant. Proc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1177\/1060028019847231","article-title":"Safety of Antithymocyte Globulin in Patients Undergoing Liver Transplantation With Livers From Donation After Circulatory Death Donors","volume":"53","author":"Jorgenson","year":"2019","journal-title":"Ann. Pharmacother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/lt.25762","article-title":"Immunosuppression in Donation After Circulatory Death Liver Transplantation: Can Induction Modify Graft Survival?","volume":"26","author":"Goldberg","year":"2020","journal-title":"Liver Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1002\/lt.21905","article-title":"Thymoglobulin Induction in Liver Transplant Recipients with a Tacrolimus, Mycophenolate Mofetil, and Steroid Immunosuppressive Regimen: A Five-Year Randomized Prospective Study","volume":"15","author":"Boillot","year":"2009","journal-title":"Liver Transplant."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/14\/4051\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:13:11Z","timestamp":1760109191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/14\/4051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":28,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["jcm13144051"],"URL":"https:\/\/doi.org\/10.3390\/jcm13144051","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,11]]}}}