Academic journal article Environmental Health Perspectives

Polychlorinated Biphenyls, Lead, and Mercury Are Associated with Liver Disease in American Adults: NHANES 2003-2004

Academic journal article Environmental Health Perspectives

Polychlorinated Biphenyls, Lead, and Mercury Are Associated with Liver Disease in American Adults: NHANES 2003-2004

Article excerpt

BACKGROUND: High-level occupational exposures to some industrial chemicals have been associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, the potential role of low-level environmental pollution on liver disease in the general population has not been evaluated.

OBJECTIVE: We determined whether environmental pollutants are associated with an elevation in serum alanine aminotransferase (ALT) activity and suspected NAFLD in U.S. adults.

METHODS: This cross-sectional cohort study evaluated adult participants without viral hepatitis, hemochromatosis, or alcoholic liver disease from the National Health and Nutrition Examination Survey (NHANES) for 2003-2004. ALT elevation was defined in men as [greater than or equal to] 37 IU/L (age 18-20 years) and [greater than or equal to] 48 IU/L (age [greater than or equal to] 21 years) and in women as [greater than or equal to] 30 IU/L (age 18-20 years) and [greater than or equal to] 31 IU/L (age [greater than or equal to] 21 years). Adjusted odds ratios (ORs) for ALT elevation were determined across exposure quartiles for 17 pollutant subclasses comprising 111 individual pollutants present with at least a 60% detection rate. Adjustments were made for age, race/ethnicity, sex, body mass index, poverty income ratio, and insulin resistance. Individual pollutants from subclasses associated with ALT elevation were subsequently analyzed.

RESULTS: The overall prevalence of ALT elevation was 10.6%. Heavy metals and polychlorinated biphenyls (PCBs) were associated with dose-dependent increased adjusted ORs for ALT elevation. Within these subclasses, increasing whole-blood levels of lead and mercury and increasing lipid-adjusted serum levels of 20 PCBs were individually associated with ALT elevation.

CONCLUSIONS: PCB, lead, and mercury exposures were associated with unexplained ALT elevation, a proxy marker of NAFLD, in NHANES 2003-2004 adult participants.

Key WORDS: environmental liver disease, hepatotoxicity, lead, mercury, NAFLD, NASH, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, PCBs, polychlorinated biphenyls, TASH. Environ Health Perspect 118:1735-1742 (2010). doi:10.1289/ebp.1002720 [Online 3 September 2010]

doi:10.1289/ebp. 1002720

The burden of liver disease has increased in the United States in parallel with the obesity epidemic, and some cases are believed to be due to nonalcoholic fatty liver disease (NAFLD) or its more advanced form, nonalcoholic steatohepatitis (NASH) (Cave et al. 2007). Serum alanine aminotransferase (ALT) is the most specific of the routinely used biomarkers for hepatocellular liver injury and disease in clinical medicine (Green and Flamm 2002). Currently, there is no serologic biomarker to confirm the diagnosis of NAFLD, but ALT elevation (above normal laboratory reference ranges) is the most common laboratory manifestation of NAFLD, and ALT elevation unexplained by viral hepatitis, ethanol, or iron overload has been used as a surrogate biomarker for NAFLD in the National Health and Nutrition Examination Survey (NHANES) (Clark 2006). Using this approach, Clark et al. (2003) reported that "unexplained ALT elevation" or "suspected NAFLD" was present in 5.4% of adult NHANES III (1988-1994) participants. Since the publication of that study, unexplained ALT elevation has been rapidly adopted by other authors to define subpopulations within NHANES with suspected NAFLD (Clark et al. 2003; Dunn et al. 2008; Liangpunsakul and Chalasani 2004, 2005).

High-level occupational exposures to industrial chemicals have been associated with liver diseases, including NAFLD (Cave et al. 2007; Cotrim et al. 1999, 2004). Recently, insulin resistance and toxicant-associated steatohepatitis (TASH), a form of NASH, were reported in nonobese chemical workers who had been highly exposed to vinyl chloride (Cave et al. 2010). However, the potential influence of low-level environmental pollution on liver disease and suspected NAFLD in the general population has not been determined. …

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