Ducatman Alan, Tan Youran, Nadeau Brian, Steenland Kyle
School of Public Health, West Virginia University, Morgantown, WV 26506-9190, USA.
Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Toxics. 2023 May 10;11(5):449. doi: 10.3390/toxics11050449.
Per- and polyfluoroalkyl substances (PFASs) including perfluorooctanoic acid (PFOA) are ubiquitous environmental contaminants. Prior analysis in the large "C8 Health Project" population defined abnormal alanine aminotransferase (ALT) with statistically derived cutoffs (>45 IU/L in men, >34 IU/L in women).
To explore the degree to which PFOA was associated with modern, clinically predictive ALT biomarker cutoffs in obese and nonobese participants, excluding those with diagnosed liver disease.
We reevaluated the relationship of serum PFOA to abnormal ALT using predictive cutoff recommendations including those of the American College of Gastroenterology (ACG). Evaluations modeled lifetime cumulative exposure and measured internal PFOA exposure.
ACG cutoff values (≥34 IU/L for males, ≥25 IU/L for females) classified 30% of males (3815/12,672) and 21% of females (3359/15,788) above ALT cutoff values. Odds ratios (OR) for above cutoff values were consistently associated with modeled cumulative and measured serum PFOA. Linear trends were highly significant. ORs by quintile showed near monotonic increases. Trends were stronger for the overweight and obese. However, all weight classes were affected.
Predictive cutoffs increase the OR for abnormal ALT results. Obesity increases ORs, yet association with abnormal ALT pertains to all weight classes. The results are discussed in context of current knowledge about the health implications of PFOA hepatotoxicity.
包括全氟辛酸（PFOA）在内的全氟和多氟烷基物质（PFASs）是普遍存在的环境污染物。在大型“C8健康项目”人群中，先前的分析通过统计学得出的临界值（男性>45 IU/L，女性>34 IU/L）定义了丙氨酸氨基转移酶（ALT）异常。
探讨在排除已诊断肝病患者的肥胖和非肥胖参与者中，PFOA与现代临床预测性ALT生物标志物临界值相关的程度。
我们使用包括美国胃肠病学会（ACG）在内的预测临界值建议，重新评估血清PFOA与ALT异常之间的关系。评估模拟了终生累积暴露量并测量了体内PFOA暴露量。
ACG临界值（男性≥34 IU/L，女性≥25 IU/L）将30%的男性（3815/12672）和21%的女性（3359/15788）分类为高于ALT临界值。高于临界值的比值比（OR）与模拟的累积和测量的血清PFOA始终相关。线性趋势非常显著。按五分位数划分的OR显示出几乎单调增加。超重和肥胖者的趋势更强。然而，所有体重类别均受到影响。
预测临界值增加了ALT结果异常的OR。肥胖会增加OR，但与ALT异常的关联适用于所有体重类别。在当前关于PFOA肝毒性对健康影响的知识背景下讨论了这些结果。
