Abstract

Background: Environmental pollutants cause liver damage and telomere shortening. Effects may vary by race/ethnicity. This study examined interactions among liver-related outcomes, telomere length, and environmental pollutants by race/ethnicity.

Methods: The study included 36,092 adults (age ≥20 years old) in the National Health and Nutrition Examination Survey (NHANES, 1999-2018) with data on blood levels of cadmium (Cd), lead (Pb) and mercury (Hg); 1,242 had data on 34 polychlorinated biphenyls (PCBs); and 7,360 had data on telomere length. Advanced liver fibrosis (LF) was defined as ALT elevation (≥40 IU/L, men; ≥31 IU/L, women) and FIB-4 ≥2.67 and/or Forns ≥6.9 and/or APRI ≥1.5. Shortened telomeres were in the 1^st quartile (Q1) of length. Associations between advanced LF and pollutants were analyzed by multivariable logistic regression (MVL); mixtures were analyzed by weighted quantile sums (WQS) models.

Results: High (Q4) blood levels of Pb were significantly associated with advanced LF in non-Hispanic (NH)-Blacks, but not in any other racial/ethnic group in MVL models adjusted for survey cycle, age, sex, BMI, smoking status, alcohol use, diabetes, and poverty: Odds ratio = 2.35, (95%CI, 1.43-3.85) (Fig 1A). Cd was associated with advanced LF in all racial/ethnic groups (Fig 1A). In WQS mixture analysis of three metals, Pb was the most significant contributor to the association between toxic exposure and advanced LF in NH-Blacks, while Cd was the most significant contributor in other groups. High (Q4) blood levels of Pb were associated with shortened telomeres in NH-Blacks and Mexican Americans (Fig 1B); Q4 blood levels of Cd were associated with shortened telomeres in NH-Whites (Fig 1B). Shorter telomeres were associated with higher risk of advanced LF (Fig 1C). In WQS mixture analysis of metals and PCBs, Cd and PCB199 were the most significant contributors to the significant association between toxic exposures and advanced LF (Fig 1D), while PCB126, Cd, and Pb were the most significant contributors to the significant association between toxic exposures and ALT elevation (Fig 1E).

Conclusion: Innovations in statistics allow mixtures to be analyzed. WQS mixture analysis of common pollutants revealed that Pb is associated with advanced LF in NH-Blacks. This hepatotoxic effect may be mediated by telomere shortening, which was associated with Pb exposure in NH-Blacks and Mexican Americans. Pollution may be contributing to liver-related healthcare disparities.