Disordered bile acid metabolism in alcohol-related hepatitis
Tyson, LD Atkinson, S Mullish, BH Pechlivanis, A Alison, M Austin, Andrew Chappell, K Forbes, SJ Forrest, EH Kilpatrick, AM
Tyson, LD
Atkinson, S
Mullish, BH
Pechlivanis, A
Alison, M
Austin, Andrew
Chappell, K
Forbes, SJ
Forrest, EH
Kilpatrick, AM
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.
MIDER Authors
Affiliations
Imperial College London; St Mary's Hospital; NIHR Biomedical Research Centre; University Hospitals of Derby and Burton NHS Foundation Trust; et al
Date
2026-03-23
Type
Article
Subject
Collections
Citation
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. Disordered Bile Acid Metabolism in Alcohol-Related Hepatitis. Aliment Pharmacol Ther. 2026 Mar 23. doi: 10.1111/apt.70616. Epub ahead of print