Ambient air pollution exposure is associated with liver fat and stiffness in Latino youth with a more pronounced effect in those with PNPLA3 genotype and more advanced liver disease

Abstract

Background: Exposure to ambient air pollutants has emerged as a risk for metabolic-dysfunction associated steatotic liver disease (MASLD).

Objectives: We sought to examine associations between short-term (prior month) and long-term (prior year) ambient air pollution exposure with hepatic fat fraction (HFF) and liver stiffness in Latino youth with obesity. A secondary aim was to investigate effect modification by patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype and liver disease severity.

Methods: Data was analyzed from 113 Latino youth (age 11-19) with obesity in Southern California. Individual exposure to particulate matter with aerodynamic diameter ≤ 2.5μm (PM_2.5), ≤ 10μm (PM₁₀), nitrogen dioxide (NO₂), 8-hour maximum ozone (8hrMax-O₃), 24-hr O₃, and redox-weighted oxidative capacity (O_x^wt) were estimated using residential address histories and United States Environmental Protection Agency air quality observations. HFF and liver stiffness were measured using magnetic resonance imaging. Linear models were used to determine associations between short-term and long-term exposure to air pollutants with HFF and liver stiffness. Modification by PNPLA3 and liver disease severity was then examined.

Results: Short-term exposure to 8hrMax-O₃ was positively associated with HFF. Relationships between air pollution exposure and HFF were not impacted by PNPLA3 genotype or liver disease severity. Long-term exposure to 8hrMax-O₃ and O_x^wt were positively associated with liver stiffness. Associations between air pollution exposure and liver stiffness depended on PNPLA3 genotype, such that individuals with GG genotypes exhibited stronger, more positive relationships between short-term exposure to PM₁₀, 8hrMax-O₃, 24-hr O_3, and O_x^wt and liver stiffness than individuals with CC/CG genotypes. In addition, relationships between short-term exposure to NO₂ and liver stiffness were stronger in those with severe liver disease.

Discussion: Air pollution exposure may be a risk factor for liver disease among Latino youth with obesity, particularly in those with other preexisting risks for liver damage.

Keywords: Air pollution; MASLD; Metabolic-dysfunction association steatotic liver disease; Ozone.

Fig. 1.

Correlation Among Short-Term and Long-Term Ambient Air Pollutants. Heatmap shows the correlation among the short-term and long-term ambient air pollutants. Pearson correlation coefficients are colored according to the strength of the correlation coefficient, and statistical significance is reported as *p<0.05, **p<0.01, and *** p<0.001.

Fig. 2.. Short Exposure to Ambient Air Pollutants were Associated with Hepatic Fat Fraction (HFF).

Multivariable linear models with robust standard errors were used to assess the associations between ambient air pollution exposure with hepatic fat fraction (HFF) after adjusting for sex (male/female), body mass index (BMI), study (HEROES/Probiotic), and season of visit (warm/cool). Plots show the raw (unadjusted) data with the best fit line derived from the multivariable linear model.

Fig. 3.

Long-Term Exposure to Ambient Air Pollutants were Associated with Greater Liver Stiffness. Multivariable linear models with robust standard errors were used to assess the associations between ambient air pollution exposure with liver stiffness after adjusting for sex (male/female), body mass index (BMI), study (HEROES/Probiotic), and season of visit (warm/cool). Plots show the raw (unadjusted) data with the best fit line derived from the multivariable linear model.

Fig. 4.

Long-Term Ambient Air Pollution Exposure is Associated with Greater Liver Stiffness Among those with Two PNPLA3 Risk Alleles. Multivariable linear models with robust standard errors were used to assess the associations between ambient air pollution exposure with liver stiffness after adjusting for sex, body mass index (BMI), season, and study. Interaction terms between exposure and PNPLA3 genotype were additionally included in each model. Plots show the raw (unadjusted) data with the best fit line derived from the multivariable linear model. Figures show that the associations between A) prior year PM₁₀ (β interaction=0.04, p-interaction=0.04), B) prior year 8hrMax-O₃ (β interaction=0.05, p-interaction=0.02), C) prior year 24hr-O₃ ((β interaction=0.08, p-interaction=0.01), and D) prior year ${\text{O}}_{\text{x}}^{\text{wt}}$ exposure (β interaction=0.11, p-interaction=0.03) with liver stiffness was stronger among those with GG genotypes of PNPLA3 (red) than those with CC/CG genotypes of PNPLA3 (blue).

Fig. 5.

Short-Term Ambient Air Pollution Exposure is Associated with Greater Liver Stiffness Among those with Liver Disease. Multivariable linear models with robust standard errors were used to assess the associations between ambient air pollution exposure with hepatic fat fraction (HFF) after adjusting for sex, body mass index (BMI), season, and study. Interaction terms between exposure and liver disease severity were additionally included in each model. Plots show the raw (unadjusted) data with the best fit line derived from the multivariable linear model. Figure shows that the MASLD with fibrosis group (red) demonstrated stronger positive associations between prior month NO₂ exposure (β interaction=0.03, p-interaction=0.04) and liver stiffness when compared to the average of the MASLD without fibrosis group (grey) and healthy liver group (blue).