Abstract 4903: Short chain per- and polyfluoroalkyl substances associate with elevated alanine aminotransferase: cross-sectional analysis results from the STRIVE cohort

Abstract Background: Although long chain, high molecular weight per- and polyfluoroalkyl substances (PFAS) (≥8 and ≥6 carbons for carboxylic and sulfonic acids; molecular weight >400 g/mol) have been associated with elevated ALT, the association of short chain, low molecular weight PFAS with elevated ALT or cirrhosis, a risk factor for hepatocellular carcinoma, remains unclear. Objectives: To examine associations of short or long chain PFAS mixtures with elevated ALT or cirrhosis and baseline factors related to PFAS. Methods: We included 349 adults aged 40-75 years from the Southern Liver Health Study (STRIVE), an ongoing longitudinal observational study. At enrollment, 135 out of 196 participants had a confirmed diagnosis of cirrhosis. We used logistic regression to examine associations between individual PFAS serum levels and elevated ALT or cirrhosis, at baseline. Quantile g-computation was used to test the associations of short or long chain PFAS mixtures with the outcomes. Linear regression examined baseline factors associated with PFAS. Results: Increasing all short chain PFAS by one quartile was associated with higher odds of elevated ALT (odds ratio: 2.20 [1.32-3.67]); no association was observed with the long chain PFAS mixture. Perfluoroheptanoate, a short-chain PFAS, was associated with both elevated ALT and cirrhosis (odds ratios: 1.53 [1.01-2.33]; 1.51 [1.01-2.27], respectively) at unadjusted P. Long chain PFAS were higher in males and linked to higher reported levels of alcohol consumption. Both long and short chain PFAS were lower in bottled water users, non-water drinkers, and current smokers compared. Perfluoropentanoic acid, a short chain PFAS, was higher in females. Conclusions: In the STRIVE cohort, higher short-chain PFAS mixture concentrations were significantly associated with elevated ALT and varied by sex and lifestyle behaviors. Citation Format: Bojung Seo, Hongxu Wang, Rachel Maguire, Yukun Liu, Beatrice Smith, Kristin Haller, David Conti, Heinz-Josef Lenz, Antonio Planchart, Giorgio Roccaro, Lesley S. Miller, Andrew Muir, Susan K. Murphy, Andrew Moon, Melissa Troester, Cynthia A. Moylan, Joellen Schildkraut, Cathrine Hoyo, Jesse A. Goodrich. Short chain per- and polyfluoroalkyl substances associate with elevated alanine aminotransferase: cross-sectional analysis results from the STRIVE cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4903.