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Lookup NU author(s): Dr Steven MassonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.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.
Author(s): Tyson LD, Atkinson S, Mullish BH, Pechlivanis A, Allison M, Austin A, Chappell K, Forbes SJ, Forrest EH, Kilpatrick AM, Liu T, Martinez-Gili L, Masson S, McPhail MJW, Nunes J, Richardson P, Rodrigo-Torres D, Ryder SD, Wright M, Patel VC, Vergis N, Holmes E, Thursz MR
Publication type: Article
Publication status: Published
Journal: Alimentary Pharmacology and Therapeutics
Year: 2026
Pages: epub ahead of print
Online publication date: 23/03/2026
Acceptance date: 04/03/2026
Date deposited: 14/04/2026
ISSN (print): 0269-2813
ISSN (electronic): 1365-2036
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1111/apt.70616
DOI: 10.1111/apt.70616
Data Access Statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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