Despite the high prevalence of alcoholic liver disease, its identification and characterization remain poor, especially in early stages such as alcoholic fatty liver disease and alcoholic steatohepatitis. This latter implies diagnostic difficulties, few therapeutic options and unclear mechanisms of action. To elucidate the metabolic alterations and pinpoint affected biochemical pathways, alcoholic steatohepatitis was simulated in vitro by exposing HepaRG cells to ethanol (IC₁₀, 368 mM) and tumor necrosis factor alpha (TNF-α, 50 ng/mL) for 24 h. This combined exposure was compared to solely ethanol-exposed as well as -nonexposed cells. Four different metabolomics platforms were used combining liquid chromatography, high-resolution mass spectrometry and drift tube ion mobility to elucidate both intracellular and extracellular metabolic alterations. Some of the key findings include the influence of TNF-α in the upregulation of hepatic triglycerides and the downregulation of hepatic phosphatidylethanolamines and phosphatidylcholines. S-Adenosylmethionine showed to play a central role in the progression of alcoholic steatohepatitis. In addition, fatty acyl esters of hydroxy fatty acid (FAHFA)-containing triglycerides were detected for the first time in human hepatocytes and their alterations showed a potentially important role during the progression of alcoholic steatohepatitis. Ethoxylated phosphorylcholine was identified as a potential new biomarker of ethanol exposure.

尽管酒精性肝病的患病率很高，但其识别和表征仍然很差，尤其是在酒精性脂肪肝和酒精性脂肪性肝炎等早期阶段。后者意味着诊断困难、治疗选择很少和作用机制不明确。_{为了阐明代谢改变并查明受影响的生化途径，通过将 HepaRG 细胞暴露于乙醇 (IC 10)}在体外模拟酒精性脂肪性肝炎, 368 mM) 和肿瘤坏死因子 α (TNF-α, 50 ng/mL) 24 小时。将这种组合暴露与单独暴露于乙醇和未暴露的细胞进行比较。使用四种不同的代谢组学平台，结合液相色谱、高分辨率质谱和漂移管离子淌度来阐明细胞内和细胞外的代谢改变。一些关键发现包括 TNF-α 对肝甘油三酯上调和肝磷脂酰乙醇胺和磷脂酰胆碱下调的影响。小号- 腺苷甲硫氨酸显示在酒精性脂肪性肝炎的进展中发挥核心作用。此外，首次在人肝细胞中检测到含有羟基脂肪酸 (FAHFA) 的甘油三酯的脂肪酰酯，它们的改变在酒精性脂肪性肝炎的进展过程中显示出潜在的重要作用。乙氧基化磷酸胆碱被确定为乙醇暴露的潜在新生物标志物。