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This underscores the necessity for developing biomarkers to assess post-transplantation mortality. Here we compared plasma trimethylamine-N-oxide (TMAO) levels with those in the general population, investigated its determinants, and interrogated its association with all-cause mortality in stable LTRs. Plasma TMAO was measured in 367 stable LTRs from the TransplantLines cohort (NCT03272841) and in 4837 participants from the population-based PREVEND cohort. TMAO levels were 35% higher in LTRs compared with PREVEND participants (4.3 vs. 3.2 \u00b5mol\/L, p &lt; 0.001). Specifically, TMAO was elevated in LTRs with metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and polycystic liver disease as underlying etiology (p &lt; 0.001 for each). Among LTRs, TMAO levels were independently associated with eGFR (std. \u03b2 = \u22120.43, p &lt; 0.001) and iron supplementation (std. \u03b2 = 0.13, p = 0.008), and were associated with mortality (29 deaths during 8.6 years follow-up; log-rank test p = 0.017; hazard ratio of highest vs. lowest tertile 4.14, p = 0.007). In conclusion, plasma TMAO is likely elevated in stable LTRs, with impaired eGFR and iron supplementation as potential contributory factors. Our preliminary findings raise the possibility that plasma TMAO could contribute to increased mortality risk in such patients, but this need to be validated through a series of rigorous and methodical studies.<\/jats:p>","DOI":"10.3390\/ijms25116031","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T03:46:49Z","timestamp":1717127209000},"page":"6031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Circulating Trimethylamine-N-Oxide Is Elevated in Liver Transplant Recipients"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9714-5809","authenticated-orcid":false,"given":"Maria Camila","family":"Trillos-Almanza","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4310-5657","authenticated-orcid":false,"given":"Mateo","family":"Chvatal-Medina","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3917-592X","authenticated-orcid":false,"given":"Margery A.","family":"Connelly","sequence":"additional","affiliation":[{"name":"Labcorp, 100 Perimeter Park, Morrisville, NC 27560, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4764-0246","authenticated-orcid":false,"given":"Han","family":"Moshage","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"TransplantLines Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-6791","authenticated-orcid":false,"given":"Stephan J. L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7900-5917","authenticated-orcid":false,"given":"Vincent E.","family":"de Meijer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4240-7506","authenticated-orcid":false,"given":"Hans","family":"Blokzijl","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3844-5254","authenticated-orcid":false,"given":"Robin P. F.","family":"Dullaart","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJMra2200923","article-title":"Liver Transplantation","volume":"389","author":"Lucey","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S178","DOI":"10.1016\/j.ajt.2023.02.006","article-title":"OPTN\/SRTR 2021 Annual Data Report: Liver","volume":"23","author":"Kwong","year":"2023","journal-title":"Am. J. Transplant."},{"key":"ref_3","first-page":"22","article-title":"Current status of liver transplantation in Europe","volume":"82S","author":"Kabacam","year":"2020","journal-title":"Int. J. 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