Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, Level 11, 12 Science Drive 2, Singapore, 117549, Singapore.
Institute of Nutrition and Health, Qingdao University, Qingdao, Shandong, China.
Metabolomics. 2018 Jan 31;14(3):26. doi: 10.1007/s11306-018-1326-z.
Chronic hepatitis B virus (HBV) infection is the main etiologic risk factor for hepatocellular carcinoma (HCC). Early studies indicated that the increase of omega-6-derived oxylipins may be involved in the pathogenesis of HBV-related HCC, yet their changes during the distinct clinical phases of chronic HBV infection remain unclear. To fill this gap, in this study we investigated the omega-6-derived oxylipin profiles in patients with three major clinical stages of chronic HBV infection (chronic hepatitis B, liver cirrhosis, and HCC).
Eighteen omega-6-derived oxylipins were quantified in serum samples of 34 patients with chronic hepatitis B, 46 patients with HBV-related liver cirrhosis, 38 patients with HBV-related HCC, and 50 healthy controls using liquid chromatography tandem mass spectrometry.
Seven oxylipins were found to be altered in patients with HBV-related liver diseases, including 9,10-dihydroxyoctadecenoic acid (9,10-DiHOME), 12,13-DiHOME, 14,15-dihydroxyeicosatrienoic acid (14,15-DiHETrE), 13-hydroxyoctadecadienoic acid (13-HODE), 12-hydroxyeicosatetraenoic acid (12-HETE), 11-HETE, and thromboxane B (TXB). Of these, three oxylipins derived from the cytochrome P450 (CYP450) pathways including 9,10-DiHOME, 12,13-DiHOME, and 14,15-DiHETrE were found to be associated with the levels of α-fetoprotein (AFP), a tumor marker. In combination with AFP, age, and gender, a combination of these seven differential oxylipins could significantly enhance the prediction of HBV-related liver diseases, particularly for liver cirrhosis (p < 0.05).
This study for the first time shows the correlations between CYP450-derived oxylipins and the progression of chronic HBV infection, and sheds a new light on the surveillance of HBV-related live diseases using oxylipins.
慢性乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）的主要病因风险因素。早期研究表明，ω-6 衍生的氧化脂质可能参与了乙型肝炎病毒相关 HCC 的发病机制，但它们在慢性 HBV 感染的不同临床阶段的变化尚不清楚。为了填补这一空白，本研究调查了三种主要的慢性 HBV 感染临床阶段（慢性乙型肝炎、肝硬化和 HCC）患者的ω-6 衍生氧化脂质谱。
使用液相色谱串联质谱法，对 34 例慢性乙型肝炎患者、46 例乙型肝炎相关肝硬化患者、38 例乙型肝炎相关 HCC 患者和 50 例健康对照者的血清样本中 18 种ω-6 衍生氧化脂质进行定量分析。
发现 7 种氧化脂质在乙型肝炎相关肝病患者中发生改变，包括 9,10-二羟基十八碳烯酸（9,10-DiHOME）、12,13-二羟基十八碳烯酸（12,13-DiHOME）、14,15-二羟基二十碳三烯酸（14,15-DiHETrE）、13-羟基十八碳二烯酸（13-HODE）、12-羟基二十碳四烯酸（12-HETE）、11-HETE 和血栓素 B（TXB）。其中，三种来源于细胞色素 P450（CYP450）途径的氧化脂质，包括 9,10-DiHOME、12,13-DiHOME 和 14,15-DiHETrE，与肿瘤标志物甲胎蛋白（AFP）水平相关。将这些氧化脂质与 AFP、年龄和性别相结合，可以显著提高乙型肝炎相关肝病，特别是肝硬化的预测能力（p<0.05）。
本研究首次显示了 CYP450 衍生氧化脂质与慢性 HBV 感染进展之间的相关性，为使用氧化脂质监测乙型肝炎病毒相关肝脏疾病提供了新的思路。
