Comparative metabolome analysis reveals higher potential of haemoperfusion adsorption in providing favourable outcome in ACLF patients
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd..
BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed.
METHODS: We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post-HA and TPE sessions on days 7 and 14 using high-resolution mass spectrometry.
RESULTS: The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p < .05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine-proline metabolism (6 metabolites) and microbial metabolism respectively (p < .05). Metabolites linked to taurine-hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post-TPE therapy (p < .05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post-HA therapy compared to TPE and SMT (p < .05). Higher baseline plasma level of 11-deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p < .05) and mortality (log-rank-p < .05). Notably, 51 of the 64 metabolite signatures (ACLF non-survivor) were reversed post-HA treatment compared to TPE and SMT(p < .05).
CONCLUSION: HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11-deoxycorticosterone level correlates with early mortality in ACLF patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:44 |
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| Enthalten in: |
Liver international : official journal of the International Association for the Study of the Liver - 44(2024), 5 vom: 05. Apr., Seite 1189-1201 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yadav, Manisha [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.04.2024 Date Revised 19.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/liv.15858 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368481697 |
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| 245 | 1 | 0 | |a Comparative metabolome analysis reveals higher potential of haemoperfusion adsorption in providing favourable outcome in ACLF patients |
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| 500 | |a Date Revised 19.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed | ||
| 520 | |a METHODS: We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post-HA and TPE sessions on days 7 and 14 using high-resolution mass spectrometry | ||
| 520 | |a RESULTS: The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p < .05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine-proline metabolism (6 metabolites) and microbial metabolism respectively (p < .05). Metabolites linked to taurine-hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post-TPE therapy (p < .05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post-HA therapy compared to TPE and SMT (p < .05). Higher baseline plasma level of 11-deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p < .05) and mortality (log-rank-p < .05). Notably, 51 of the 64 metabolite signatures (ACLF non-survivor) were reversed post-HA treatment compared to TPE and SMT(p < .05) | ||
| 520 | |a CONCLUSION: HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11-deoxycorticosterone level correlates with early mortality in ACLF patients | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a extracorporeal liver support system | |
| 650 | 4 | |a haemoperfusion adsorption | |
| 650 | 4 | |a metabolomic profile | |
| 650 | 4 | |a safety and efficacy | |
| 650 | 4 | |a therapeutic plasma exchange | |
| 650 | 7 | |a Tryptophan |2 NLM | |
| 650 | 7 | |a 8DUH1N11BX |2 NLM | |
| 650 | 7 | |a Bile Acids and Salts |2 NLM | |
| 650 | 7 | |a Desoxycorticosterone |2 NLM | |
| 650 | 7 | |a 40GP35YQ49 |2 NLM | |
| 700 | 1 | |a Maiwal, Rakhi |e verfasserin |4 aut | |
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| 700 | 1 | |a Bindal, Vasundhra |e verfasserin |4 aut | |
| 700 | 1 | |a Mathew, Babu |e verfasserin |4 aut | |
| 700 | 1 | |a Pandey, Sushmita |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Satender Pal |e verfasserin |4 aut | |
| 700 | 1 | |a Tevathia, Harsh Vardhan |e verfasserin |4 aut | |
| 700 | 1 | |a Maras, Jaswinder Singh |e verfasserin |4 aut | |
| 700 | 1 | |a Sarin, Shiv Kumar |e verfasserin |4 aut | |
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