Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease
Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease
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DOI：
10.1007/s10620-019-05638-y
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发表时间：
2019-07-01
影响因子：
3.1
通讯作者：
Schnabl, Bernd
中科院分区：
文献类型：
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作者：
Gao, Bei;Lang, Sonja;Schnabl, Bernd
背景酒精相关性肝病是世界范围内最常见的慢性肝病之一。酒精相关性肝病的发病机制还不清楚。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，尽管如此，氧脂素在酒精相关性肝病中的研究尚不充分。目的：（1）描述酒精使用障碍和酒精性肝炎患者中生物活性-3和-6多不饱和脂肪酸代谢物的模式，（2）确定酒精相关性肝病患者血清氧脂素与临床参数的相关性。方法我们进行了全面的液相色谱串联质谱分析。（LC-MS/MS）分析血清和粪便oxlipins来自-6花生四烯酸，-3二十碳五烯酸，和二十二碳六烯酸在一个患者队列与酒精相关的liverdiseases.ResultsOur结果显示，酒精使用障碍和酒精性肝炎患者的血清oxlipin档案的深刻变化相比，非酒精性对照。氧脂素与临床参数的斯皮尔曼相关性显示，不同血清氧脂素与肠通透性、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，较高水平的血清20-HETE显着相关的白蛋白减少，增加肝脂肪变性，多形核细胞浸润，90天mortals.ConclusionsPatients与酒精相关的肝病有不同的oxylipin配置文件。需要进一步的研究来确认氧脂素作为疾病的生物标志物或将氧脂素与疾病的发病机制联系起来。
BackgroundAlcohol-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.Aims(1) To characterize the patterns of bioactive -3 and -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.MethodsWe performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from -6 arachidonic acid, -3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease.ResultsOur 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.ConclusionsPatients 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.