Serum aryl hydrocarbon receptor activity is associated with survival in patients with alcohol-associated hepatitis
Copyright © 2024 American Association for the Study of Liver Diseases..
BACKGROUND AND AIMS: Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites, which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in patients with AH.
APPROACH AND RESULTS: The study included 74 controls without AUD, 97 patients with AUD, and 330 patients with AH from 2 different multicenter cohorts (InTeam: 134, AlcHepNet: 196). Serum AhR activity was evaluated using an AhR reporter assay with HepG2-Lucia cells incubated with serum for 24 hours. Serum AhR activity was significantly higher in patients with AH compared with both controls (1.59 vs. 0.96-fold change, p < 0.001) and patients with AUD (1.59 vs. 0.93, p < 0.001). In both AH cohorts, patients with AhR activity ≥ 2.09 had significantly lower cumulative survival rates at 30, 60, 90, and 180 days compared to those with AhR activity < 2.09. When serum AhR activity was used to further stratify patients with severe AH, the cumulative 30, 60, 90, and 180-day survival rates for patients with severe AH and the AhR activity ≥ 2.09 group were all significantly lower than those with an AhR activity < 2.09 group.
CONCLUSIONS: Serum AhR activity was significantly higher in patients with AH compared with controls and individuals with AUD, and this increased activity was associated with higher mortality. Consequently, serum AhR activity holds potential as a prognostic marker.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Hepatology (Baltimore, Md.) - (2024) vom: 20. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yamazaki, Tomoo [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 11.04.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1097/HEP.0000000000000777 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368675106 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368675106 | ||
| 003 | DE-627 | ||
| 005 | 20240411232339.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240222s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1097/HEP.0000000000000777 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1372.xml |
| 035 | |a (DE-627)NLM368675106 | ||
| 035 | |a (NLM)38377466 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yamazaki, Tomoo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Serum aryl hydrocarbon receptor activity is associated with survival in patients with alcohol-associated hepatitis |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 11.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024 American Association for the Study of Liver Diseases. | ||
| 520 | |a BACKGROUND AND AIMS: Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites, which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in patients with AH | ||
| 520 | |a APPROACH AND RESULTS: The study included 74 controls without AUD, 97 patients with AUD, and 330 patients with AH from 2 different multicenter cohorts (InTeam: 134, AlcHepNet: 196). Serum AhR activity was evaluated using an AhR reporter assay with HepG2-Lucia cells incubated with serum for 24 hours. Serum AhR activity was significantly higher in patients with AH compared with both controls (1.59 vs. 0.96-fold change, p < 0.001) and patients with AUD (1.59 vs. 0.93, p < 0.001). In both AH cohorts, patients with AhR activity ≥ 2.09 had significantly lower cumulative survival rates at 30, 60, 90, and 180 days compared to those with AhR activity < 2.09. When serum AhR activity was used to further stratify patients with severe AH, the cumulative 30, 60, 90, and 180-day survival rates for patients with severe AH and the AhR activity ≥ 2.09 group were all significantly lower than those with an AhR activity < 2.09 group | ||
| 520 | |a CONCLUSIONS: Serum AhR activity was significantly higher in patients with AH compared with controls and individuals with AUD, and this increased activity was associated with higher mortality. Consequently, serum AhR activity holds potential as a prognostic marker | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Kouno, Tetsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Hsu, Cynthia L |e verfasserin |4 aut | |
| 700 | 1 | |a Hartmann, Phillipp |e verfasserin |4 aut | |
| 700 | 1 | |a Mayo, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xinlian |e verfasserin |4 aut | |
| 700 | 1 | |a Stärkel, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Bosques-Padilla, Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Verna, Elizabeth C |e verfasserin |4 aut | |
| 700 | 1 | |a Abraldes, Juan G |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Robert S |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Vargas, Victor |e verfasserin |4 aut | |
| 700 | 1 | |a Altamirano, Jose |e verfasserin |4 aut | |
| 700 | 1 | |a Caballería, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Shawcross, Debbie L |e verfasserin |4 aut | |
| 700 | 1 | |a Louvet, Alexandre |e verfasserin |4 aut | |
| 700 | 1 | |a Lucey, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Mathurin, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia-Tsao, Guadalupe |e verfasserin |4 aut | |
| 700 | 1 | |a Bataller, Ramon |e verfasserin |4 aut | |
| 700 | 1 | |a Schnabl, Bernd |e verfasserin |4 aut | |
| 700 | 0 | |a AlcHepNet Investigators |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Hepatology (Baltimore, Md.) |d 1983 |g (2024) vom: 20. Feb. |w (DE-627)NLM012603902 |x 1527-3350 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:20 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1097/HEP.0000000000000777 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 20 |c 02 | ||