Air pollution impacts metabolic pathways linked to metabolic dysfunction-associated steatotic liver disease (MASLD), highlighting environmental contributions to liver disease

Ran S et al, J Hepatol. 2025;82(4):560-570
The authors used air pollution data combined with metabolic analysis from the UK Biobank to investigate the impact of pollution on liver disease. They identified metabolic changes in around 280,000 participants that were linked to air pollution exposure and demonstrated a potentially causal link between these changes and the development of MASLD. This research provides strong evidence of how air pollution influences metabolic pathways leading to liver disease. 

Background and aims: Air pollution is a significant public health issue and an important risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), though the underlying mechanisms of this association are unknown. Herein, the authors aimed to identify metabolic signatures associated with exposure to ambient air pollution and to explore their associations with the risk of MASLD. Methods: Data from the UK Biobank cohort were utilized. Annual mean concentrations of PM2.5, PM10, NO2 and NOx were assessed for each participant using bilinear interpolation. The elastic net regression model was used to identify metabolites associated with 4 air pollutants and to construct metabolic signatures. Associations between air pollutants, metabolic signatures and MASLD were analyzed using Cox models. Mendelian randomization (MR) analysis was used to examine potential causality. Mediation analysis was employed to examine the role of metabolic signatures in the association between air pollutants and MASLD. Results: A total of 244,842 participants from the UK Biobank were included in this analysis. The authors identified 87, 65, 76, and 71 metabolites as metabolic signatures of PM2.5, PM10, NO2, and NOx, respectively. Metabolic signatures were associated with risk of MASLD, with hazard ratios (HRs) and 95% confidence intervals [CIs] of 1.10 (1.06–1.14), 1.06 (1.02–1.10), 1.24 (1.20–1.29) and 1.14 (1.10–1.19), respectively. The 4 pollutants were associated with increased risk of MASLD, with HRs (95% CIs) of 1.03 (1.01–1.05), 1.02 (1.01–1.04), 1.01 (1.01–1.02) and 1.01 (1.00–1.01), respectively. MR analysis indicated an association between PM2.5, NO2 and NOx-related metabolic signatures and MASLD. Metabolic signatures mediated the association of PM2.5, PM10, NO2 and NOx with MASLD.

Conclusions: PM2.5, PM10, NO2 and NOx-related metabolic signatures appear to be associated with metabolic dysfunction-associated steatotic liver disease (MASLD). These signatures mediated the increased risk of MASLD associated with PM2.5, PM10, NO2 and NOx.