Disordered Bile Acid Metabolism in Alcohol‐Related Hepatitis
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Alcohol-related hepatitis (AH) is characterised by acute cholestasis and liver dysfunction in patients consuming alcohol. AIMS: To define the bile acid (BA) profile in AH compared to decompensated alcohol-related cirrhosis (DC) and healthy controls (HC). METHODS: Serum and faecal BAs were measured by UHPLC-MS; FGF19 by ELISA; RNA-sequencing data obtained from liver biopsies; serum cytokines and growth factors quantified by multiplex immunoassay. Hepatocyte growth factor (HGF) was applied to primary human hepatocytes (PHH) and BA transporter expression was assessed by RT-qPCR. RESULTS: In two cohorts (Cohort 1: 164 AH, 63 DC, 36 HC; Cohort 2: 94 AH, 175 DC, 72 HC), total serum BAs were highest in AH (median concentration 186.0 μM vs. 64.5 DC vs. 5.0 HC), driven by elevated conjugated primary BAs (182.0 μM vs. 54.0 vs. 2.2). Unconjugated primary BAs were highest in DC. Serum BAs distinguished AH from DC (Cohort 1 AUROC 0.964; Cohort 2 0.922; p < 0.001). Faecal BAs were reduced in AH (0.47 mg/g vs. 1.11 DC vs. 2.64 HC); serum FGF19 elevated (5835 pg/mL AH vs. 865 jaundiced DC [bilirubin > 80 μmol/L]). Serum conjugated BAs correlated negatively with NTCP expression (n = 25, Spearman's rho -0.432, p = 0.031). CYP7A1 was below the limit of detection. HGF was elevated in AH (7899 pg/mL vs. 2607 DC, p < 0.001). HGF treatment reduced PHH BSEP expression. CONCLUSION: Serum conjugated primary BAs accumulate in AH. Elevated HGF may detrimentally affect the hepatoprotective adaptive reduction in NTCP/increase in BSEP seen in cholestasis, contributing to the AH BA profile.
DOI: 10.1111/apt.70616
Authors: Luke D. Tyson, Stephen Atkinson, Benjamin H. Mullish, Alexandros Pechlivanis, Michael Allison, Andrew Austin, Katie Chappell, Stuart J. Forbes, Ewan H. Forrest, Alastair M. Kilpatrick, Tong Liu, Laura Martinez‐Gili, Steven Masson, Mark J. W. McPhail, Joao Nunes, Paul Richardson, Daniel Rodrigo‐Torres, Stephen D. Ryder, Mark Wright, Vishal C. Patel, Nikhil Vergis, Elaine Holmes, Mark R. Thursz
Institutions: Imperial College Healthcare NHS Trust, St Mary's Hospital, Imperial College London, GlaxoSmithKline (United Kingdom), Addenbrooke's Hospital, NIHR Cambridge Biomedical Research Centre, Royal Derby Hospital, MRC Centre for Regenerative Medicine, University of Edinburgh, Glasgow Royal Infirmary, University of Glasgow, Newcastle upon Tyne Hospitals NHS Foundation Trust, NIHR Newcastle Biomedical Research Centre, Newcastle University, King's College Hospital, Royal Liverpool University Hospital, Nottingham University Hospitals NHS Trust, University of Nottingham, Queen's Medical Centre, Nottingham Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Foundation for Liver Research
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,250
Awards: The influence of gut microbiome-related lipids and glycans upon intestinal colonisation, and the impact of faecal microbiota transplant, Establishing MRC-NIHR Phenome Centre, a world leading high-throughput metabolic phenotyping centre for humanpopulation disease-risk biomarker discovery., G3665202723, The clinical effectiveness and cost-effectiveness of STeroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2x2 factorial, randomised controlled trial, MICA: Minimising Mortality from Alcoholic Hepatitis
OpenAlex ID: W7140142675