Editorial: Air Pollution Associated With Mortality Among Chronic Hepatitis B Patients

Abstract

Recent evidence suggests that air pollution also contributes to the development of metabolic dysfunction associated with steatosis liver disease (MASLD), progression of cirrhosis, incidence of hepatocellular carcinoma (HCC), and liver-related mortality beyond lung disease [1-5]. Particulate matter 2.5 (PM2.5) and NOx are the most extensively studied in liver disease. A meta-analysis investigating the association between air pollution and the incidence of MASLD and progression of cirrhosis showed that PM2.5, NOx, PM10, PM2.5–10, PM1, and air pollution from solid fuel combustion increased the risk of developing NAFLD and related cirrhosis [3]. Another systematic review on air pollution and HCC indicated that PM2.5 was also significantly associated with the incidence of HCC, whereas the associations with other air pollutants (nitrogen oxide (NOx)) and HCC and incidence of HCC and liver-related mortality remain inconclusive and require further research [4].

This study examines the association between air pollution and mortality in chronic hepatitis B (CHB) patients receiving nucleos(t)ide analog therapy, emphasising environmental exposures as a significant factor in liver disease progression. A significant finding of this study is the association between NOx exposure and increased mortality risk in CHB patients. Unlike prior research that predominantly examined metabolic disorders or HCC [6, 7], this study demonstrates that NOx levels exceeding 25.5 ppb are associated with a 2.5-fold increase in mortality risk among cirrhotic CHB patients. This finding underscores the necessity of incorporating environmental risk factors into liver disease management, particularly for high-risk populations. Furthermore, the study highlights the long-term impact of air pollution on CHB survival. Over a 10-year period, CHB patients residing in high NOx exposure regions exhibited a mortality rate of 37.6%, compared to 18.6% in lower-exposure areas. This contrast emphasises the need to include environmental factors in CHB treatment strategies. NOx exposure not only affects liver-related mortality but also increases overall mortality, highlighting the importance of a comprehensive approach to CHB care that mitigates environmental risks.

Another recent evidence suggests that certain populations may be more susceptible to the air pollution. Previous studies have reported that exposure to oxidative gaseous air pollutants is associated with an increase in liver fat content and the risk of developing MASLD, particularly showing a strong association in Hispanic participants [8]. This includes individuals with pre-existing liver conditions or those with genetic predispositions to liver cancer. A study conducted on 69 young adults from the Meta-AIR cohort examined the association between PNPLA3-I148M genotype, oxidative gaseous air pollutant exposure, and liver fat accumulation. After short-term exposure to oxidative gaseous air pollutants, participants with the GG genotype showed a 71.8% increase in liver fat, whereas those with the CC/CG genotype showed only a 2.4% increase [5].

While the mechanisms by which air pollution affects the onset and progression of liver diseases are not yet clear [9], oxidative stress induced by PM2.5 is known to activate hepatic immune cells, particularly Kupffer cells, amplifying inflammatory responses such as TNF-α, IL-6, and IL-1β. This leads to liver cells becoming more susceptible to mutations, genomic instability, and apoptosis through repeated cycles of damage and repair. The development of fatty liver disease, fibrosis progression, and HCC due to air pollution is presumed to result from an increase in liver inflammation induced by air pollutants. However, due to the complexity of environmental exposures and potential confounding factors, more well-designed prospective studies are required to establish air pollutants as definitive carcinogens for liver cancer.

Hyo Young Lee: writing – original draft. Dae Won Jun: conceptualization, funding acquisition, writing – review and editing.

The authors declare no conflicts of interest.

This article is linked to Jang et al paper. To view this article, visit https://doi.org/10.1111/apt.70019.