PM2.5 air pollution exposure and nonalcoholic fatty liver disease

From the VoPham Group, Public Health Sciences Division

One of the most common causes of chronic liver disease is nonalcoholic fatty liver disease (NAFLD). NAFLD contributes to liver-related mortality and morbidity and is defined as the accumulation of fat in the liver, also known as a hepatic steatosis. The prevalence and mortality rates of NAFLD have increased in recent years. NAFLD has risk factors such as obesity, diabetes, and dyslipidemia; however, environmental factors that contribute to NAFLD are unclear. Women and Hispanic persons are more likely to be diagnosed with NAFLD compared to their male counterparts or other ethnic groups, respectively. Also, people who live in the southern and western regions of the US are more likely to develop NAFLD than those who live in the northern and eastern regions of the US. Identifying modifiable risk factors could help decrease the morbidity and mortality of NAFLD. 

Fine particulate matter air pollution <2.5 µm in diameter (PM2.5) has been associated with cardiovascular disease, cancer, and multiple system organ failure. PM2.5 pollutants consist primarily of a mixture of chemicals originating from fossil fuel combustion. Recent literature using rodent and other animal models reported a positive association between PM2.5 and NAFLD.  Population-based research has reported positive and inverse associations between PM2.5 and NAFLD.  The VoPham Group, led by Dr. Trang VoPham, Assistant Professor of Epidemiology in the Public Health Sciences Division of Fred Hutch, is the first to examine this association in a large-scale, nationwide study with multiple years of information onPM2.5 exposure. The objective of the study was to determine the association between ambient PM2.5 exposure and NAFLD among hospitalized patients. The study was published in the journal Environmental Research.

The VoPham group used the Nationwide Inpatient Sample (NIS) from 2001 to 2011, a nationally representative healthcare administrative database in the US that includes hospital discharge records. Dr. VoPham elaborated on the methods, “To conduct this study, we used geospatial science methods to link two large-scale databases: (1) ambient PM2.5 concentrations (from the Environmental Protection Agency) and (2) the NIS inpatient healthcare administrative database. The exposure data was estimated from census tract-level annual PM2.5 levels for each hospitalization year. Multivariable logistic regression was utilized to measure the association between census-tract level PM2.5 exposure and the odds of NAFLD in hospitalized patients. Effect modification was evaluated by NAFLD disparities such as age, sex, race/ethnicity, diabetes, obesity, smoking, and region.

The study included over 45,433,392 hospitalizations from 2001-2011. After adjusting for covariates, higher census tract-level ambient PM2.5 exposure was associated with increased odds of NAFLD among hospitalized patients. Also, the associations between PM2.5 exposure and NAFLD among hospitalized patients were modified by age, race/ethnicity, diabetes, smoking, and region.  The link between PM2.5 exposure and NAFLD hospitalization was stronger associated among patients 45 years and/or older, non-Hispanic White or non-Hispanic Asian or Pacific Islander. Also, stronger associations were shown among those hospitalized in the Midwest and Western regions of the US – this could be due regional differences in coal-fired power plants and wood burning practices.

Graphical Representation of Air pollution exposure and nonalcoholic fatty liver disease
Figure 1. Air pollution exposure and nonalcoholic fatty liver disease Image from Dr. Trang VoPham

“Strengths of this study included examining of a large number of hospitalizations spanning multiple years and applying geospatial methods to objectively assess PM2.5 exposure levels in the population. Further, the NIS database provided valuable information for the statistical analyses, including data on patient demographics, hospital characteristics, and hospital discharge diagnosis codes used to identify NAFLD and other clinical conditions”, said Dr. VoPham. Not only was this the first study to evaluate PM2.5 exposure and NAFLD hospitalizations on a large scale, but the study also evaluated potential confounding and effect modification using a large number of covariates. Dr. VoPham explained her next steps, “We will build on the findings from this paper through a K01 study funded by the NIH/NIDDK to examine air pollution exposure and health disparities for NAFLD and liver cancer using electronic health records (EHRs) (K01 DK125612; PI VoPham). This K01 study improves on some limitations of this paper, including using high-resolution geocoded residential addresses and PM2.5 exposure modeling methods to assess ambient exposures, and applying EHR algorithms (that have been validated against medical review) to examine incident NAFLD and liver cancer cases. “

This research was supported by the National Institutes of Health (NIH) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Dr. Trang VoPham and Dr. Jason Mendoza contributed to this work.

VoPham T, Kim NJ, Berry K, Mendoza JA, Kaufman JD, Ioannou GN. PM2. 5 air pollution exposure and nonalcoholic fatty liver disease in the Nationwide Inpatient Sample. Environmental Research. 2022 Jun 7:113611.