{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:25:08Z","timestamp":1773833108826,"version":"3.50.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:00:00Z","timestamp":1726617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:00:00Z","timestamp":1726617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Klinikum der Universit\u00e4t M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bilirubin is one of the most frequently used laboratory values to monitor critically ill patients with cholestatic liver dysfunction. Besides bilirubin, toxic bile acids (TBAs), which may cause severe organ damage, are typically elevated. A correlation between both parameters seems plausible, but data are lacking. The aim was to investigate whether there is a correlation between bilirubin and TBAs in patients\u2019 blood and whether a compareable reduction can be observed during the use of the adsorber CytoSorb (CS). As part of the Cyto-SOLVE study (NCT04913298), 16 critically ill patients with cholestatic liver dysfunction, bilirubin concentration\u2009&gt;\u200910\u00a0mg\/dl, continuous kidney replacement therapy and CS-application were investigated. Bilirubin and TBA concentrations were measured from arterial blood at defined time points (before start, after 6 and 12\u00a0h). Relative reduction (RR) was calculated using the formula<jats:inline-formula><jats:tex-math>$$\\:\\:{\\boldsymbol{RR}}\\:{\\boldsymbol{\\left(\\%\\right)}}=\\frac{{\\boldsymbol{concentration\\left(pre-post\\right)}}}{{\\boldsymbol{concentration\\left(pre\\right)}}}*{\\boldsymbol{100}}$$<\/jats:tex-math><\/jats:inline-formula>. A moderate to high correlation between bilirubin and TBA concentration at all defined timepoints (r<jats:sub>start<\/jats:sub>=0.64, <jats:italic>p<\/jats:italic>\u2009=\u20090.008; r<jats:sub>6h<\/jats:sub>\u2009=\u20090.85, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, r<jats:sub>12h<\/jats:sub>\u2009=\u20090.72, <jats:italic>p<\/jats:italic>\u2009=\u20090.002) was observed. In the first six hours of CS-application, a significant elimination of TBA (median TBA: 30.8\u219220.1\u00b5mol\/l, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and bilirubin (median bilirubin: 17.1\u219211.9\u00a0mg\/dl, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) was observed. The median RR after 6\u00a0h was 26.1% and 39.8% for bilirubin and TBA, respectively. No further reduction was observed after 12\u00a0h (RR<jats:sub>bilirubin<\/jats:sub>: \u2013 0.6%, RR<jats:sub>TBA<\/jats:sub>: 1.8%). There was an at least moderate correlation between bilirubin and TBA in patients with cholestatic liver dysfunction. Therefore, bilirubin seems to be a suitable surrogate parameter for TBA elimination during CytoSorb application.<\/jats:p>","DOI":"10.1038\/s41598-024-72676-6","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T17:05:57Z","timestamp":1726765557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Correlation of bilirubin and toxic bile acids in critically ill patients with cholestatic liver dysfunction and adsorber application"],"prefix":"10.1038","volume":"14","author":[{"given":"Caroline","family":"Gr\u00e4fe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Graf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vassilissa","family":"Wustrow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Liebchen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Conter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Paal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Habler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Scharf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,9,18]]},"reference":[{"key":"72676_CR1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jcrc.2017.01.017","volume":"40","author":"C Pierrakos","year":"2017","unstructured":"Pierrakos, C. et al. Increased mortality in critically ill patients with mild or moderate hyperbilirubinemia. J. Crit. Care40, 31\u201335 (2017).","journal-title":"J. Crit. Care"},{"issue":"1","key":"72676_CR2","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13613-017-0272-7","volume":"7","author":"T Horvatits","year":"2017","unstructured":"Horvatits, T. et al. Circulating bile acids predict outcome in critically ill patients. Ann. Intensive Care7(1), 48 (2017).","journal-title":"Ann. Intensive Care"},{"issue":"14","key":"72676_CR3","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.3748\/wjg.15.1677","volume":"15","author":"MJ Perez","year":"2009","unstructured":"Perez, M. J. & Briz, O. Bile-acid-induced cell injury and protection. World J. Gastroenterol.15(14), 1677\u20131689 (2009).","journal-title":"World J. Gastroenterol."},{"issue":"4","key":"72676_CR4","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.molmed.2023.01.007","volume":"29","author":"L Vitek","year":"2023","unstructured":"Vitek, L., Hinds, T. D., Stec, D. E. & Tiribelli, C. The physiology of bilirubin: health and disease equilibrium. Trends Mol. Med.29(4), 315\u2013328 (2023).","journal-title":"Trends Mol. Med."},{"key":"72676_CR5","unstructured":"Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes.pdf>."},{"issue":"1","key":"72676_CR6","doi-asserted-by":"publisher","first-page":"10190","DOI":"10.1038\/s41598-021-89712-4","volume":"11","author":"C Scharf","year":"2021","unstructured":"Scharf, C. et al. Successful elimination of bilirubin in critically ill patients with acute liver dysfunction using a cytokine adsorber and albumin dialysis: a pilot study. Sci. Rep.11(1), 10190 (2021).","journal-title":"Sci. Rep."},{"key":"72676_CR7","doi-asserted-by":"crossref","unstructured":"Riva, I., Marino, A., Valetti, T. M., Marchesi, G. & Fabretti, F. Extracorporeal liver support techniques: a comparison. J. Artif. Organs (2023).","DOI":"10.1007\/s10047-023-01409-9"},{"issue":"3","key":"72676_CR8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.tjem.2018.08.001","volume":"18","author":"H Akoglu","year":"2018","unstructured":"Akoglu, H. User\u2019s guide to correlation coefficients. Turk. J. Emerg. Med.18(3), 91\u201393 (2018).","journal-title":"Turk. J. Emerg. Med."},{"issue":"2","key":"72676_CR9","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1097\/SHK.0000000000001836","volume":"57","author":"J Juschten","year":"2022","unstructured":"Juschten, J. et al. Incidence, clinical characteristics and outcomes of early hyperbilirubinemia in critically ill patients: insights from the mars study. Shock57(2), 161\u2013167 (2022).","journal-title":"Shock"},{"issue":"3","key":"72676_CR10","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1097\/MOG.0000000000000354","volume":"33","author":"JI Sullivan","year":"2017","unstructured":"Sullivan, J. I. & Rockey, D. C. Diagnosis and evaluation of hyperbilirubinemia. Curr. Opin. Gastroenterol.33(3), 164\u2013170 (2017).","journal-title":"Curr. Opin. Gastroenterol."},{"issue":"1","key":"72676_CR11","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1186\/s13054-022-04163-1","volume":"26","author":"R Perez","year":"2022","unstructured":"Perez, R. et al. Critical care hepatology: definitions, incidence, prognosis and role of liver failure in critically ill patients. Crit. Care26(1), 289 (2022).","journal-title":"Crit. Care"},{"issue":"1","key":"72676_CR12","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s00134-015-4054-0","volume":"42","author":"M Jenniskens","year":"2016","unstructured":"Jenniskens, M., Langouche, L., Vanwijngaerden, Y.-M., Mesotten, D. & Van den Berghe, G. Cholestatic liver (dys)function during sepsis and other critical illnesses. Intensive Care Med.42(1), 16\u201327 (2016).","journal-title":"Intensive Care Med."},{"issue":"6","key":"72676_CR13","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/S1590-8658(02)80033-0","volume":"34","author":"ME Guicciardi","year":"2002","unstructured":"Guicciardi, M. E. & Gores, G. J. Bile acid-mediated hepatocyte apoptosis and cholestatic liver disease. Dig. Liver Disease34(6), 387\u2013392 (2002).","journal-title":"Dig. Liver Disease"},{"issue":"4","key":"72676_CR14","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1097\/MEG.0000000000001043","volume":"30","author":"AM Voiosu","year":"2018","unstructured":"Voiosu, A. M. et al. Total bile acid levels are associated with left atrial volume and cardiac output in patients with cirrhosis. Eur. J. Gastroenterol. Hepatol.30(4), 392\u2013397 (2018).","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"issue":"1","key":"72676_CR15","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13613-020-00795-0","volume":"11","author":"K Ocskay","year":"2021","unstructured":"Ocskay, K. et al. Uncertainty in the impact of liver support systems in acute-on-chronic liver failure: a systematic review and network meta-analysis. Ann. Intensive Care11(1), 10 (2021).","journal-title":"Ann. Intensive Care"},{"issue":"2","key":"72676_CR16","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1152\/physrev.00049.2019","volume":"101","author":"A Perino","year":"2021","unstructured":"Perino, A., Demagny, H., Velazquez-Villegas, L. & Schoonjans, K. Molecular physiology of bile acid signaling in health, disease, and aging. Physiol. Rev.101(2), 683\u2013731 (2021).","journal-title":"Physiol. Rev."},{"issue":"10","key":"72676_CR17","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1177\/03913988221116135","volume":"45","author":"WF Hui","year":"2022","unstructured":"Hui, W. F., Cheung, W. L., Chung, F. S., Leung, K. K. Y. & Ku, S. W. The successful application of hemoadsorption for extracorporeal liver support in a child with acute liver failure. Int. J. Artif. Organs45(10), 878\u2013882 (2022).","journal-title":"Int. J. Artif. Organs"},{"issue":"2","key":"72676_CR18","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1177\/1751143718772789","volume":"20","author":"VD Dhokia","year":"2019","unstructured":"Dhokia, V. D., Madhavan, D., Austin, A. & Morris, C. G. Novel use of cytosorb haemadsorption to provide biochemical control in liver impairment. J. Intensive Care Soc.20(2), 174\u2013181 (2019).","journal-title":"J. Intensive Care Soc."},{"key":"72676_CR19","doi-asserted-by":"crossref","unstructured":"Popescu, M. et al. Artificial liver support with cytosorb and mars in liver failure: a retrospective propensity matched analysis. J. Clin. Med. ; 12(6). (2023).","DOI":"10.3390\/jcm12062258"},{"issue":"1","key":"72676_CR20","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1159\/000508810","volume":"50","author":"A Dominik","year":"2021","unstructured":"Dominik, A. & Stange, J. Similarities, differences, and potential synergies in the mechanism of action of albumin dialysis using the mars albumin dialysis device and the cytosorb hemoperfusion device in the treatment of liver failure. Blood Purif.50(1), 119\u2013128 (2021).","journal-title":"Blood Purif."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-72676-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-72676-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-72676-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T10:02:00Z","timestamp":1726912920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-72676-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,18]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["72676"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-72676-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,18]]},"assertion":[{"value":"21 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was obtained from the ethical review committee of the Ludwig-Maximilians-Universit\u00e4t (registration number 21\u2013236).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"CS got speaker fees from CytoSorbents Europe GmbH. UL received consulting fees from CytoSorbents Europe GmbH. All other authors do not having any competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21762"}}