2. Academic Validation
  3. Serum aryl hydrocarbon receptor activity is associated with survival in patients with alcohol-associated hepatitis

Serum aryl hydrocarbon receptor activity is associated with survival in patients with alcohol-associated hepatitis

  • Hepatology. 2024 Feb 20. doi: 10.1097/HEP.0000000000000777.
Tomoo Yamazaki 1 2,  Tetsuya Kouno 1,  Cynthia L Hsu 1 3,  Phillipp Hartmann 4 5,  Susan Mayo 1 3,  Xinlian Zhang 6,  Peter Stärkel 7,  Francisco Bosques-Padilla 8,  Elizabeth C Verna 9,  Juan G Abraldes 10,  Robert S Brown Jr 11,  Victor Vargas 12 13,  Jose Altamirano 12,  Juan Caballería 13 14,  Debbie L Shawcross 15,  Alexandre Louvet 16,  Michael R Lucey 17,  Philippe Mathurin 16,  Guadalupe Garcia-Tsao 18,  Ramon Bataller 19,  Bernd Schnabl 1 3,  AlcHepNet Investigators
Affiliations

Affiliations

  • 1 Department of Medicine, University of California San Diego, La Jolla, California, USA.
  • 2 Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan.
  • 3 Department of Medicine, VA San Diego Healthcare System, San Diego, California, USA.
  • 4 Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
  • 5 Division of Gastroenterology, Hepatology & Nutrition, Rady Children's Hospital San Diego, San Diego, CA, USA.
  • 6 Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
  • 7 Department of Hepatology and Gastroenterology, St. Luc University Hospital, Catholic University of Louvain, Brussels, Belgium.
  • 8 Hospital Universitario, Departamento de Gastroenterología, Universidad Autonoma de Nuevo Leon, Monterrey, México.
  • 9 Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
  • 10 Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada.
  • 11 Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, USA.
  • 12 Liver Unit, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • 13 Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
  • 14 Liver Unit, Hospital Clinic, Barcelona, Spain.
  • 15 Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, UK.
  • 16 Service des Maladies de L'appareil Digestif et Unité INFINITE 1286, Hôpital Huriez, Lille, France.
  • 17 Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, WI, USA.
  • 18 Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA, and Section of Digestive Diseases, VA-CT Healthcare System, West Haven, CT, USA.
  • 19 Liver Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
PMID: 38377466 DOI: 10.1097/HEP.0000000000000777
Abstract

Background: 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 AH patients.

Methods: The study included 74 controls without alcohol use disorder (AUD), 97 patients with AUD and 330 AH patients from two 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.

Results: 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.

Conclusion: 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.

Figures
Products