Association between long-term exposure to PM₁₀ and metabolic dysfunction-associated steatotic liver disease (MASLD) in subjects with disturbed metabolic homeostasis and genotypes at risk.

Abstract

Poor information exists on the role of air pollutants as possible predictors of liver fat over-storage in subjects with increased clinical and genetic risk for MASLD. In 140 cardio-metabolic patients we assessed Hepatic Steatosis Index (HSI), grading of MASLD, gene variants MBOAT7 rs641738, PNPLA3 rs738409, TM6SF2 rs58542926, diet and exposure to particulate matter <10 µm (PM₁₀) and to nitrogen dioxide (NO₂) in the prior 6 months. About two-thirds of patients had MASLD. HSI depended on PM₁₀ but not on NO₂ levels. A stepwise backward regression confirmed sex, age, waist circumference, type 2 diabetes as significant predictors of the HSI in the whole group. Exposure to PM₁₀ was an additional predictor only in subjects with homozygous mutations. Carriers of homozygous variants showed the highest HSI, rate and grade of steatosis when living in areas with the highest exposure to PM₁₀, as compared with wild-type or heterozygous subjects. Generalized additive models showed a nonlinear association between HSI and PM₁₀ levels in the whole group and in subjects with- but not in those without homozygous variants. In patients with homozygous SNPs, HSI was negatively correlated with the adherence to Mediterranean diet. Mild chronic exposure to PM₁₀ is as an additional, independent predictor of liver fat over-storage in subjects with cardio-metabolic disorders and with increased genetic risk for MASLD. Besides specific genotypes and phenotypes, chronic exposure to PM₁₀ should be also taken into account in future studies considering risk stratification, and in selecting subjects with MASLD for inclusion in clinical trials.