Associations of MAFLD subtypes and air pollutants with multi-system morbidity and all-cause mortality: A prospective cohort study.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) and air pollution are both significant health concerns. However, their combined effects on multi-system morbidity and all-cause mortality remain poorly understood.

Methods: We analyzed data from 434,417 UK Biobank participants, categorizing them into four groups: non-MAFLD, MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obesity. To evaluate the long-term effects of air pollution exposure, we used time-varying Cox proportional hazard models to assess four air pollutants: particulate matter with an aerodynamic diameter < 2.5 μm (PM), PM, nitrogen dioxide (NO), and nitrogen oxides (NO). We examined the associations between these air pollutants, MAFLD subtypes, and their joint impact on multi-system morbidity and all-cause mortality. Furthermore, we explored the additive and multiplicative interactions between air pollutants and MAFLD subtypes.

Results: At baseline, 15,325 participants were classified as MAFLD-diabetes, 3341 as MAFLD-lean, and 140,934 as MAFLD-overweight/obesity. Among these groups, MAFLD-diabetes was most strongly associated with adverse outcomes compared to other subtypes. Air pollution exposure had a synergistic effect on cirrhosis risk across all MAFLD subtypes, with the most pronounced effects observed for PM [relative excess risk due to interaction (RERI): 2.10 (0.94, 3.26)] and NO [RERI:1.85 (0.67, 3.04)] in MAFLD-lean group. Positive additive and multiplicative interactions between air pollutants and MAFLD subtypes were also observed for coronary artery disease (CAD), with the exception of nitrogen oxide in the MAFLD-lean group. Additionally, only the MAFLD-diabetes demonstrated significant positive additive interactions with all four air pollutants in relation to chronic kidney disease (CKD).

Conclusions: This study highlights the distinct impacts of MAFLD subtypes on multi-system morbidity and all-cause mortality, underscoring the critical need for targeted prevention and treatment strategies, particularly for individuals with MAFLD-diabetes. Our findings reveal significant additive and synergistic effects of air pollution exposure on the risks of cirrhosis, CAD, and CKD among MAFLD patients.