Growing evidences supported that arsenic exposure contributes to non-alcoholic fatty liver disease (NAFLD) risk, but findings were still inconsistent. Additionally, once absorbed, arsenic is methylated into monomethyl and dimethyl arsenicals. However, no studies investigated the association of arsenic metabolism with NAFLD. Our objectives were to evaluate the associations of arsenic exposure and arsenic metabolism with NAFLD prevalence. We conducted a case-control study with 1790 participants derived from Dongfeng-Tongji cohort and measured arsenic species (arsenite, arsenate, monomethylarsonate [MMA], dimethylarsinate [DMA], and arsenobetaine) in urine. Arsenic exposure (∑As) was defined as the sum of inorganic arsenic (iAs), MMA, and DMA. Arsenic metabolism was evaluated as the proportions of inorganic-related species (iAs%, MMA%, and DMA%) and methylation efficiency ratios (primary methylation index [PMI], secondary methylation index [SMI]). NAFLD was diagnosed by liver ultrasound. Logistic regression was used to evaluate the associations. The median of ∑As was 13.24 μg/g creatinine. The ∑As showed positive and nonlinear association with moderate/severe NAFLD (OR: per log-SD = 1.33, 95% CI: [1.03,1.71]; = 0.021). The iAs% (OR: per SD = 1.16, 95% CI: [1.03,1.30]) and SMI (OR: per log-SD = 1.16, 95% CI: [1.03,1.31]) showed positive while MMA% (OR: per SD = 0.80, 95% CI: [0.70,0.91]) and PMI (OR: per log-SD = 0.86, 95% CI: [0.77,0.96]) showed inverse associations with NAFLD. Moreover, the ORs (95% CI) of NAFLD for each 5% increase in iAs% was 1.36 (1.17,1.58) when MMA% decreased and 1.07 (1.01,1.13) when DMA% decreased; and for each 5% increase in MMA%, it was 0.74 (0.63,0.86) and 0.79 (0.69,0.91) when iAs% and DMA% decreased, respectively. The results suggest that inorganic arsenic exposure is positively associated with NAFLD risk and arsenic methylation efficiency plays a role in the NAFLD. The findings provide clues to explore potential interventions for the prevention of NAFLD. Prospective studies are needed to validate our findings.

中文翻译：

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砷暴露和砷代谢与非酒精性脂肪肝风险的关系

越来越多的证据表明砷暴露会增加非酒精性脂肪肝 (NAFLD) 风险，但研究结果仍然不一致。此外，砷一旦被吸收，就会甲基化成一甲基砷和二甲基砷。然而，没有研究调查砷代谢与 NAFLD 的关系。我们的目标是评估砷暴露和砷代谢与 NAFLD 患病率的关系。我们对来自东风-同济队列的 1790 名参与者进行了一项病例对照研究，并测量了尿液中的砷形态（亚砷酸盐、砷酸盐、一甲基胂酸盐 [MMA]、二甲基胂酸盐 [DMA] 和砷甜菜碱）。砷暴露（ΣAs）定义为无机砷（iAs）、MMA 和 DMA 的总和。砷代谢通过无机相关物种的比例（iAs％、MMA％和DMA％）和甲基化效率比（初级甲基化指数[PMI]、次级甲基化指数[SMI]）进行评估。NAFLD 通过肝脏超声诊断。使用逻辑回归来评估关联性。ΣAs 的中位数为 13.24 μg/g 肌酐。ΣAs 显示与中度/重度 NAFLD 呈正向和非线性相关（OR：每 log-SD = 1.33，95% CI：[1.03,1.71]；= 0.021）。iAs%（OR：每 SD = 1.16，95% CI：[1.03,1.30]）和 SMI（OR：每 log-SD = 1.16，95% CI：[1.03,1.31]）显示阳性，而 MMA%（OR ：每 SD = 0.80，95% CI：[0.70,0.91]）和 PMI（OR：每 log-SD = 0.86，95% CI：[0.77,0.96]）与 NAFLD 呈负相关。此外，当MMA％降低时，iAs％每增加5％，NAFLD的OR（95％CI）为1.36（1.17，1.58）；当DMA％降低时，NAFLD的OR（95％CI）为1.07（1.01，1.13）；MMA%每增加5%，当iAs%和DMA%减少时，分别为0.74（0.63，0.86）和0.79（0.69，0.91）。结果表明，无机砷暴露与 NAFLD 风险呈正相关，砷甲基化效率在 NAFLD 中发挥作用。这些发现为探索预防 NAFLD 的潜在干预措施提供了线索。需要前瞻性研究来验证我们的发现。