Urinary Volatile Organic Compound Metabolites Are Associated With MASLD/MASH in Humans and Induce Steatosis in Liver Organoids.

Authors

Laurens A van Kleef, Xincheng Li, Pengfei Li, Ibrahim Ayada, Yasir J Abozaid, Jesse Pustjens, Marike Wabbijn, Geert Bezemer, Mohsen Ghanbari, Luc van der Laan, Harry L A Janssen, Frank Tacke, Qiuwei Pan, Willem P Brouwer

Published in

Liver international : official journal of the International Association for the Study of the Liver. Volume 46. Issue 8. Pages e70783.

Abstract

Volatile organic compound (VOC) exposure is an environmental health concern and could, through the liver exposome, be associated with metabolic dysfunction associated steatotic liver disease (MASLD) progression.
We analysed NHANES 2017-2020, a U.S. population-based cohort with controlled attenuation parameter (CAP), liver stiffness measurement (LSM) and urinary VOC metabolites. Participants with viral hepatitis, excess alcohol use or missing urine creatinine were excluded. MASLD was defined as CAP ≥ 275 dB/m with metabolic dysfunction, at-risk MASH as FAST ≥ 0.35 and increased LSM as ≥ 8 kPa. Weighted quantile sum (WQS) regression assessed associations between VOC metabolites and outcomes, adjusting for age, sex, smoking and alcohol. Phenylglyoxylic acid (PGA) and mandelic acid (MA) were further examined using logistic regression for the MA/(MA and PGA) ratio and human liver organoids.
The cohort comprised 2004 participants (41.4% MASLD, 5.4% at-risk MASH, 9.7% LSM ≥ 8 kPa). Higher VOC metabolite levels were associated with increased risk of MASLD (aOR 1.47 per quartile, 95% CI 1.06-2.04) and at-risk MASH (aOR 2.69 per quartile, 95% CI 1.23-5.87), primarily driven by N-Acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA) and N-Acetyl-S-(3-hydroxy-1-methylpropyl)-L-cysteine (HMPMA), with inverse associations driven by PGA. No significant associations were found for increased LSM, yet a higher MA/(MA + PGA) ratio was associated with increased risk for at-risk MASH and LSM ≥ 8 kPa. In human liver organoids, PGA exposure increased lipid droplet number and size.
Urinary VOC metabolites show distinct associations with MASLD and at-risk MASH in the general population. CEMA and HMPMA were associated with increased risk, consistent with prior links to metabolic dysfunction. PGA induced steatosis in liver organoids, suggesting poor metabolising of styrene and ethylbenzene and intracellular PGA accumulation.

PMID:
42411650
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.