INTRODUCTION Exposures to volatile organic compounds and metals have previously been associated with liver diseases including steatohepatitis, although more data are needed. Benzene, toluene, ethylbenzene, xylenes, styrene (BTEXS) and metals were measured in blood samples collected between May 2012-July 2013 from volunteers participating in home visits for the Gulf Long-term Follow-up (GuLF) Study. This cross-sectional analysis evaluates associations of exposure biomarkers with serum liver injury and adipocytokine biomarkers in a sample of 214 men. METHODS Adult nonsmoking men without a history of liver disease or heavy alcohol consumption were included. The serologic disease biomarkers evaluated were the hepatocellular injury biomarker, cytokeratin 18 [whole (CK18 M65) and caspase-cleaved fragment (CK18 M30)]; and adipocytokines. Confounder-adjusted beta coefficients were determined using linear regression models for the overall sample (primary endpoints) and for obesity-classified sub-groups (secondary endpoints). A product interaction term between the exposure of interest and a dichotomized indicator of obesity was included to determine the disease modifying effects of obesity on the biomarker associations. RESULTS The study sample was 57% white and 51% obese. In the overall sample, lead was positively associated with CK18 M30 (β = 21.7 ± 6.0 (SE), p = 0.0004); IL-1β (β = 32.8 ± 5.2, p < 0.0001); IL-6 (β = 72.8 ± 18.3, p = 0.0001); and IL-8 (β = 140.8 ± 42.2, p = 0.001). Cadmium exposures were associated with increased IL-1β (β = 77.8 ± 26.3, p = 0.003) and IL-8 (β = 419.5 ± 201.2, p = 0.04). There were multiple significant interactions between obesity and exposure to lead, cadmium, benzene and toluene in relation to outcome biomarkers. Among obese participants (n = 108), benzene, lead, and cadmium were each positively associated with CK18 M30, IL-1β, IL-6, and IL-8. In obese subjects, lead was also inversely associated with leptin, and toluene was positively associated with IL-1β. CONCLUSION For the overall sample, heavy metal exposures were associated with liver injury (lead only) and/or systemic inflammation (lead and cadmium). Obesity modified the associations between BTEXS and heavy metal exposures on several of the outcome variables. In the obesity subgroup, liver injury was positively associated with lead, cadmium and benzene exposures; systemic inflammation was increased with lead, cadmium, benzene, and toluene exposures; and leptin was inversely associated with lead exposures. The cross-sectional design of this study makes it difficult to determine causality, and all results should be interpreted cautiously. Nonetheless, the potential impact of exposures to lead, cadmium, benzene and toluene in steatohepatitis, an obesity-associated inflammatory liver disease, warrants further investigation.

中文翻译：

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海湾国家居民的血液 BTEXS 和重金属水平与肝损伤和全身炎症有关。

简介 此前曾认为接触挥发性有机化合物和金属与包括脂肪性肝炎在内的肝脏疾病有关，但还需要更多数据。对 2012 年 5 月至 2013 年 7 月期间参加海湾长期随访 (GuLF) 研究家访的志愿者采集的血液样本中的苯、甲苯、乙苯、二甲苯、苯乙烯 (BTEXS) 和金属进行了检测。该横断面分析评估了 214 名男性样本中暴露生物标志物与血清肝损伤和脂肪细胞因子生物标志物的关联。方法 纳入无肝病史或酗酒史的成年不吸烟男性。评估的血清学疾病生物标志物是肝细胞损伤生物标志物、细胞角蛋白18[完整(CK18 M65)和半胱天冬酶切割片段(CK18 M30)]；和脂肪细胞因子。使用线性回归模型确定总体样本（主要终点）和肥胖分类亚组（次要终点）的混杂因素调整β系数。包括感兴趣的暴露和肥胖二分指标之间的产品相互作用项，以确定肥胖对生物标志物关联的疾病改变作用。结果 研究样本中 57% 是白人，51% 是肥胖者。在整个样本中，铅与 CK18 M30 呈正相关（β = 21.7 ± 6.0 (SE)，p = 0.0004）；IL-1β（β = 32.8 ± 5.2，p < 0.0001）；IL-6（β = 72.8 ± 18.3，p = 0.0001）；和 IL-8（β = 140.8 ± 42.2，p = 0.001）。镉暴露与 IL-1β（β = 77.8 ± 26.3，p = 0.003）和 IL-8（β = 419.5 ± 201.2，p = 0.04）增加相关。肥胖与铅、镉、苯和甲苯暴露之间存在多种与结果生物标志物相关的显着相互作用。在肥胖参与者 (n = 108) 中，苯、铅和镉分别与 CK18 M30、IL-1β、IL-6 和 IL-8 呈正相关。在肥胖受试者中，铅也与瘦素呈负相关，而甲苯与 IL-1β 呈正相关。结论 对于整个样本，重金属暴露与肝损伤（仅铅）和/或全身炎症（铅和镉）相关。肥胖改变了 BTEXS 与重金属暴露在几个结果变量上的关联。在肥胖亚组中，肝损伤与铅、镉和苯暴露呈正相关；铅、镉、苯会增加全身炎症，和甲苯暴露；瘦素与铅暴露呈负相关。这项研究的横断面设计使得确定因果关系变得困难，所有结果都应谨慎解释。尽管如此，接触铅、镉、苯和甲苯对脂肪性肝炎（一种与肥胖相关的炎症性肝病）的潜在影响值得进一步研究。