New research published in the Journal of Hepatology suggests that long-term exposure to ambient air pollution may increase the risk of metabolic-associated fatty liver disease (MAFLD), especially in those with unhealthy lifestyles and central obesity (1).
MAFLD, also known as non-alcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in Australia and worldwide (2). Due to its steadily increasing prevalence and increasingly young age at diagnosis, it represents a growing challenge in terms of prevention and treatment. Its rising prevalence parallels that of obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (3). Currently, the incidence of MAFLD is estimated to be between 20% and 50% in adults, and 5% and 10% in children (4,5).
MAFLD is a complex disease involving interactions among genetic, metabolic, and environmental factors and the gut microbiome. The current understanding of the disease involves excessive hepatic accumulation of lipids resulting from an imbalance between fatty acid input/output. This imbalance is due to changes in diet and lifestyle associated with high energy uptake, sedentary lifestyle, and insulin resistance (6,7). The progress of MAFLD involves multiple hits beginning with the accumulation of fat (fatty liver or steatosis). Excess hepatic lipid accumulation increases the vulnerability of the liver to cellular insults such as oxidative stress and inflammatory responses (8). If left untreated, MAFLD can lead to serious complications like liver fibrosis (scarring), cirrhosis, liver failure and liver cancer, as well as cardiovascular and metabolic issues (7).
In parallel to the rising MAFLD epidemic, ambient air pollution has attracted much public health concern globally due to increased morbidity and mortality (9). Air pollutants of major concern include particulate matter, carbon monoxide, ozone, nitrogen dioxide and sulphur dioxide. More than 90% of the world's population live in places with atmospheric exposures exceeding WHO air quality guidelines, and 4.2 million deaths every year occur due to exposure to outdoor air pollution (9).
Several studies have indicated that ambient air pollution is detrimentally related to many metabolic-related health outcomes, including dyslipidaemia (10,11), elevated fasting blood glucose (12), obesity (13,14), metabolic syndrome (15) and TD2M (16). However, epidemiological evidence linking air pollution exposure and MAFLD is limited.
The current cross-sectional study included 90,086 participants recruited in China from 2018 to 2019. Patients were evaluated for MAFLD based on hepatic steatosis diagnosed radiographically and the presence of overweight/obese status, diabetes, or metabolic dysregulation.
Validated spatiotemporal models were used to estimate residence-specific levels of air pollutants, including particulate matter with aerodynamic diameters ≤1 µm (PM1), ≤2 µm (PM2.5), and ≤10 µm (PM10), and nitrogen dioxide (NO2). In addition, logistic regression models were used to investigate the association between long-term exposure to air pollution and the odds of MAFLD and assess the potential modifying effects of demographics, lifestyle, central obesity, and diabetes status.
Results showed increased exposure levels in the four air pollutants were significantly correlated with an increased risk for MALFD. For each 10 µg/m3 increase in air pollutants, the likelihood of MAFLD increased by 13% for PM1, 29% for PM2.5, 11% for PM10 and 15% for NO2.
The results from stratified analyses indicated that the risk for MALFD from air pollutant exposure was greater in men, alcohol drinkers and current and previous smokers, as well as those who consume a high-fat diet and those with central obesity. Physical activity did not modify the associations between air pollution and MAFLD.
Although the specific mechanisms underlying the association between air pollution and MAFLD remain uncertain, evidence from animal studies provides some insight. PM2.5 exposure inhibits the expression of peroxisome proliferator-activated receptor (PPAR)γ and PPARα, causing hepatic steatosis, inflammation, and insulin resistance (17). Furthermore, PM2.5 exposure triggers oxidative stress and an inflammatory response which contributes to abnormal hepatic function (18) and induces collagen synthesis by hepatic stellate cells, resulting in hepatic fibrosis (19).
Limitations
This study has some limitations. Firstly, cross-sectional study findings cannot establish a causal inference between long-term air pollution exposure and the prevalence of MAFLD. Secondly, the air pollution concentrations were estimated at participants' residential addresses, which may have led to an inaccurate assessment of exposure levels.
Conclusions
The current study indicates that particulate pollution and NO2 exposure are associated with an increased risk of MAFLD. The associations observed in this study add to the growing evidence of air pollution's detrimental effects on metabolic function and related organs. Furthermore, given the coexistence of high air pollution and the rapid rise in MAFLD prevalence, the results are significant to public health and highlight an urgent need for future studies to investigate the extent to which air pollution control strategies can reduce the burden of MAFLD.
