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      Extracorporeal adsorption of protective and toxic bile acids and bilirubin in patients with cholestatic liver dysfunction: a prospective study

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          Abstract

          Background

          The release of toxic bile acids (BAs) in the blood of critically ill patients with cholestatic liver dysfunction might lead to the damage of various organs. Their extracorporeal elimination using the cytokine adsorber Cytosorb ® (CS) (adsorption of especially hydrophobic molecules < 60 kDa) might be promising, but data proving a potential adsorption are missing so far.

          Methods

          The prospective Cyto-SOVLE study (NCT04913298) included 20 intensive care patients with cholestatic liver dysfunction, continuous kidney replacement therapy, total bilirubin concentration > 10 mg/dl and the application of CS into the dialysis circuit. Bilirubin and different BAs were measured pre- and post-CS at defined timepoints (10 min, 1, 3, 6, and 12 h after initiation). Relative reduction (RR, %) was calculated with: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1-\left(\frac{\mathrm{concentration} (\mathrm{pre}-\mathrm{post})}{\mathrm{concentration} (\mathrm{pre})}\right)*100$$\end{document} .

          Results

          The median RR for total and conjugated bilirubin after initiation was − 31.8% and − 30.3%, respectively, and decreased to − 4.5% and − 4.8% after 6 h. A high initial RR was observed for the toxic BAs GCA (− 97.4%), TCA (− 94.9%), GCDCA (− 82.5%), and TCDCA (− 86.0%), decreasing after 6 h to − 32.9%, − 32.7%, − 12.8%, and − 14.3%, respectively. The protective hydrophilic BAs showed a comparable RR after initiation (UDCA: − 77.7%, GUDCA: − 83.0%, TUDCA: − 91.3%) dropping after 6 h to − 7.4%, − 8.5%, and − 12.5%, respectively.

          Conclusions

          Cytosorb ® can adsorb bilirubin and toxic as well as protective BAs. However, a fast saturation of the adsorber resulting in a rapid decrease of the RR was observed. Furthermore, no relevant difference between hydrophobic toxic and hydrophilic protective BAs was detected regarding the adsorption amount. The clinical benefit or harm of the BA adsorption needs to be evaluated in the future.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13613-023-01198-7.

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          Most cited references28

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          Bile Acid Metabolism in Liver Pathobiology.

          Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism. The gut-to-liver axis plays a critical role in the regulation of enterohepatic circulation of bile acids, bile acid pool size, and bile acid composition. Bile acids control gut bacteria overgrowth, and gut bacteria metabolize bile acids to regulate host metabolism. Alteration of bile acid metabolism by high-fat diets, sleep disruption, alcohol, and drugs reshapes gut microbiome and causes dysbiosis, obesity, and metabolic disorders. Gender differences in bile acid metabolism, FXR signaling, and gut microbiota have been linked to higher prevalence of fatty liver disease and hepatocellular carcinoma in males. Alteration of bile acid homeostasis contributes to cholestatic liver diseases, inflammatory diseases in the digestive system, obesity, and diabetes. Bile acid-activated receptors are potential therapeutic targets for developing drugs to treat metabolic disorders.
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            Comments on 'KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease'.

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              Bile-acid-induced cell injury and protection

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                Author and article information

                Contributors
                Christina.Scharf@med.uni-muenchen.de
                Journal
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                2110-5820
                9 November 2023
                9 November 2023
                2023
                : 13
                : 110
                Affiliations
                [1 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Department of Anesthesiology, , LMU Hospital, ; Marchioninistrasse 15, 81377 Munich, Germany
                [2 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Institute of Laboratory Medicine, , LMU Hospital, ; Munich, Germany
                Article
                1198
                10.1186/s13613-023-01198-7
                10635921
                37943350
                21d06ac3-29c3-434d-b063-2102975f5c8c
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 June 2023
                : 27 September 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003042, Else Kröner-Fresenius-Stiftung;
                Award ID: 2021_EKEA.101
                Award Recipient :
                Funded by: Universitätsklinik München (6933)
                Categories
                Research
                Custom metadata
                © La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF) 2023

                Emergency medicine & Trauma
                bile acids,cholestasis,critically ill patients,cytosorb®,cholestatic liver failure,mass spectrometry

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