Short-chain per- and polyfluoroalkyl substances associate with elevated alanine aminotransferase: Cross-sectional analysis results from the STRIVE cohort.

BACKGROUND: The impact of short-chain, low molecular weight polyfluoroalkyl substances (PFAS) and long-chain, high molecular weight PFAS on elevated alanine aminotransferase (ALT) remains unclear. Additionally, demographic and behavioral factors influencing PFAS levels in the U.S. population are not well understood. OBJECTIVES: To examine (1) associations between short- and long-chain PFAS mixtures and elevated ALT, and (2) participant characteristics linked to PFAS levels. METHODS: This study included 378 adults (196 with detailed liver disease evaluations and 135 with cirrhosis), aged 40-75 years, from the Southern Liver Health Study (STRIVE), an ongoing prospective cohort. Logistic regression assessed associations between serum PFAS and elevated ALT. Quantile g-computation evaluated PFAS mixture effects, while linear regression identified demographic and behavioral factors linked to PFAS levels. RESULTS: A one-quartile increase in short-chain PFAS mixture levels was associated with higher odds of elevated ALT (adjusted odds ratio [aOR], 95 % confidence interval [CI]: 2.14, 1.31-3.50; P = 0.002) and higher log-transformed ALT levels (adjusted β, 95 % CI: 0.09, 0.01-0.17; P = 0.02). Long-chain PFAS mixtures showed no significant association. Individually, perfluoroheptanoic acid (a short-chain PFAS) (aOR, 95 % CI: 1.51, 1.001-2.27; P = 0.049) and perfluorohexanesulfonic acid (a long-chain PFAS) (aOR, 95 % CI: 1.53, 1.08-2.15; P = 0.015) were positively associated with elevated ALT. PFAS levels were lower in bottled water users but higher in current alcohol users. Males and older individuals exhibited higher long-chain PFAS levels, whereas non-water drinkers and current everyday smokers had lower levels of long-chain PFAS. DISCUSSION: Higher short-chain PFAS mixture levels were linked to elevated ALT, with individual PFAS levels varying by sex and lifestyle factors. Limiting short-chain PFAS exposure may help prevent liver injury.

Duke Scholars

Author Cynthia Ann Moylan Medicine, Gastroenterology

Author Andrew Joseph Muir Medicine, Gastroenterology

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Author Joellen Martha Schildkraut Family Medicine and Community Health, Prevention Research

Author Kara Wegermann Medicine, Gastroenterology