Associations between Historically Modeled Retrospective Serum Perfluorooctanoic Acid Concentrations and Liver Function in a Highly Exposed Community Open Access

Abstract

Background: People living or working in the Mid-Ohio Valley were exposed to perfluorooctanoic acid (PFOA) released by a chemical plant for over 50 years. Prior research on this population has found associations between PFOA exposure and liver function; however, these analyses have been cross-sectional, making causal inference difficult to assess.

Objectives: We assessed the association between historically modeled retrospective PFOA and liver function, as measured by alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), and direct bilirubin, in a population with elevated PFOA exposure.

Methods: C8 Health Project (C8HP) participants were recruited to enroll in a follow-up study conducted from 2008 to 2011. Of the 40,145 individuals agreeing to participate, a total of 30,723 with retrospective exposure estimates were included in this analysis. Cumulative PFOA exposure was derived from individual estimates of annual PFOA serum concentrations, which were based on residential and work history, plant emissions, and a fate-transport model. Linear regression models were used to estimate associations between PFOA exposure and natural log (ln)-transformed concentrations of ALT, GGT, and direct bilirubin. Logistic regression models were used to examine the relationship between PFOA exposure and abnormal levels of ALT, GGT, and direct bilirubin. PFOA was examined as a continuous log-linear measure and in quintiles.

Results: Estimated cumulative ln-PFOA and estimated 2005/2006 ln-PFOA were associated with ln-ALT levels in linear regression models (cumulative PFOA coefficient: 0.012, 95% CI 0.008, 0.016; 2005/2006 PFOA coefficient: 0.012, 95% CI 0.009, 0.016) and with abnormal ALT levels in logistic regression models (cumulative PFOA: OR 1.04, 95% CI 1.01, 1.07; 2005/2006 PFOA: OR 1.04, 95% CI 1.01, 1.07). Relationships with direct bilirubin were inconsistent across analyses. Associations with GGT were mostly consistent with the null, but there was some indication of a positive association among women only.

Conclusions: These results show a positive association between PFOA serum concentrations and serum ALT levels, which is consistent with findings of a prior C8HP cross-sectional study examining the relationship between PFOA exposure and liver function. Results indicate that an association between PFOA and ALT is not an artifact of reverse causation and that PFOA exposure may have harmful effects on liver function.

Table of Contents

BACKGROUND....................................................................................... 1

METHODS............................................................................................. 10

Study population........................................................................... 10

Data collection and laboratory methods............................................ 11

Measurement of liver function biomarkers and covariates.................... 11

Exposure estimation....................................................................... 12

Statistical analysis.......................................................................... 13

RESULTS............................................................................................... 15

DISCUSSION......................................................................................... 18

REFERENCES......................................................................................... 23

TABLES AND FIGURES............................................................................ 28

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology
Keyword	Perfluorooctanoic Acid C8 Health Population ALT PFOA liver function bilirubin GGT
Committee Chair / Thesis Advisor	Darrow, Lyndsey, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs

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