Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA.
Dig Dis Sci. 2019 Jul;64(7):1878-1892. doi: 10.1007/s10620-019-05638-y. Epub 2019 May 10.
Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease.
(1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease.
We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease.
Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality.
Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.
酒精性肝病是全球最常见的慢性肝病之一。酒精性肝病发病机制中的相关机制尚不清楚。氧化脂质在许多生物过程和病理条件中起着至关重要的作用。然而，氧化脂质在酒精性肝病中的研究还不够充分。
（1）描述酒精使用障碍和酒精性肝炎患者中生物活性ω-3 和 ω-6 多不饱和脂肪酸代谢产物的模式，（2）确定与酒精性肝病患者临床参数相关的血清氧化脂质。
我们对酒精性肝病患者的血清和粪便氧化脂质进行了全面的液相色谱-串联质谱（LC-MS/MS）分析，这些氧化脂质来源于 ω-6 花生四烯酸、ω-3 二十碳五烯酸和二十二碳六烯酸。
与非酒精性对照组相比，酒精使用障碍和酒精性肝炎患者的血清氧化脂质谱发生了深刻的改变。氧化脂质与临床参数的斯皮尔曼相关性表明，不同血清氧化脂质与肠道通透性、天冬氨酸转氨酶、胆红素、白蛋白、国际标准化比值、血小板计数、脂肪变性、纤维化和终末期肝病模型评分之间存在联系。特别是，血清 20-HETE 水平升高与白蛋白降低、肝脂肪变性增加、多形核细胞浸润和 90 天死亡率增加显著相关。
酒精性肝病患者的氧化脂质谱不同。需要进一步的研究来确认氧化脂质作为疾病生物标志物或将氧化脂质与疾病发病机制联系起来。
