School of Marine Sciences, Nanjing University of Information Science and Technology, Nanjing 210044, China.
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Biomolecules. 2021 Feb 14;11(2):281. doi: 10.3390/biom11020281.
Alcohol-related liver disease is one of the most prevalent liver diseases in the United States. Early stages of alcohol-related liver disease are characterized by accumulation of triglycerides in hepatocytes. Alcoholic hepatitis is a severe form of alcohol-related liver disease associated with significant morbidity and mortality. We sought to identify patients who are at greatest risk of death using serum lipids. First, we performed lipidomics analysis on serum samples collected from 118 patients with alcoholic hepatitis to identify lipid markers that are associated with high risk of death. Next, we performed gene set enrichment analysis on liver transcriptomics data to identify dysregulated lipid metabolism in patients who received liver transplantation. Finally, we built a random forest model to predict 30-day mortality using serum lipids. A total of 277 lipids were annotated in the serum of patients with alcoholic hepatitis, among which 25 were significantly different between patients in the deceased and alive groups. Five chemical clusters were significantly altered between the two groups. In particular, acylcarnitine cluster was enriched in the deceased group. Several hepatic lipid metabolism pathways were dysregulated in patients with alcoholic hepatitis who received liver transplantation. The mRNA expression of genes involved in the fatty acid transport into mitochondria and β-oxidation were also dysregulated. When predicting 30-day mortality in alcoholic hepatitis patients using serum lipids, we found that the area under the curve achieved 0.95. Serum lipids such as acylcarnitines may serve as biomarkers to identify alcoholic hepatitis patients at the greatest risk of death.
酒精性肝病是美国最常见的肝病之一。酒精性肝病的早期阶段特征是肝细胞中甘油三酯的积累。酒精性肝炎是一种严重的酒精性肝病，与显著的发病率和死亡率相关。我们试图使用血清脂质来识别死亡风险最高的患者。首先，我们对 118 例酒精性肝炎患者的血清样本进行了脂质组学分析，以确定与高死亡风险相关的脂质标志物。接下来，我们对接受肝移植的患者的肝转录组学数据进行了基因集富集分析，以确定脂质代谢的失调。最后，我们构建了一个随机森林模型，使用血清脂质来预测 30 天死亡率。在酒精性肝炎患者的血清中注释了 277 种脂质，其中 25 种在死亡组和存活组之间存在显著差异。两组之间有 5 个化学簇发生了显著改变。特别是酰基辅酶 A 簇在死亡组中富集。接受肝移植的酒精性肝炎患者的几个肝脂质代谢途径发生失调。参与脂肪酸向线粒体转运和β-氧化的基因的 mRNA 表达也发生失调。当使用血清脂质来预测酒精性肝炎患者的 30 天死亡率时，我们发现曲线下面积达到了 0.95。酰基辅酶 A 等血清脂质可能作为生物标志物，用于识别死亡风险最高的酒精性肝炎患者。
