State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 2 Nanwei Road, Beijing, 100050, China.
Anal Bioanal Chem. 2014 Jan;406(2):555-64. doi: 10.1007/s00216-013-7479-8. Epub 2013 Nov 20.
Chronic hepatitis C virus (HCV) infection is a global health issue. Although its progression is reported to be closely associated with lipids, the way in which the plasma lipidome changes during the development of chronic HCV infection in humans is currently unknown. Using an improved quantitative high-throughput lipidomic platform, we profiled 284 lipids in human plasma samples obtained from healthy controls (n = 11) and patients with chronic HCV infection (n = 113). The intrahepatic inflammation grade (IG) of liver tissue was determined by biopsy. Two types of mass spectrometers were integrated into a single lipidomic platform with a wide dynamic range. Compared with previous methods, the performance of this method was significantly improved in terms of both the number of target sphingolipids identified and the specificity of the high-resolution mass spectrometer. As a result, 44 sphingolipids, one diacylglycerol, 43 triglycerides, 24 glycerophosphocholines, and 5 glycerophospho-ethanolamines were successfully identified and quantified. The lipid profiles of individuals with chronic HCV infection were significantly different from those of healthy individuals. Several lipids showed significant differences between mild and severe intrahepatic inflammation grades, indicating that they could be utilized as novel noninvasive indicators of intrahepatic IG. Using multivariate analysis, healthy controls could be discriminated from HCV patients based on their plasma lipidome; however, patients with different IGs were not well discriminated. Based on these results, we speculate that variations in lipid composition arise as a result of HCV infection, and are caused by HCV-related digestive system disorders rather than progression of the disease.
慢性丙型肝炎病毒 (HCV) 感染是一个全球性的健康问题。虽然其进展据报道与脂质密切相关，但人类慢性 HCV 感染发展过程中血浆脂质组如何变化目前尚不清楚。本研究使用改进的高通量定量脂质组学平台，对来自健康对照者（n=11）和慢性 HCV 感染患者（n=113）的人血浆样本中的 284 种脂质进行了分析。通过肝活检确定肝组织内炎症等级（IG）。两种类型的质谱仪被整合到一个具有宽动态范围的单一脂质组学平台中。与以前的方法相比，该方法在鉴定的鞘脂数量和高分辨率质谱仪的特异性方面的性能都得到了显著提高。结果成功鉴定和定量了 44 种鞘脂、1 种二酰基甘油、43 种甘油三酯、24 种甘油磷酸胆碱和 5 种甘油磷酸乙醇胺。慢性 HCV 感染个体的脂质谱与健康个体明显不同。几种脂质在轻度和重度肝内炎症等级之间存在显著差异，表明它们可以作为肝内 IG 的新型非侵入性指标。通过多元分析，可以根据患者的血浆脂质组学将健康对照者与 HCV 患者区分开来；然而，不同 IG 的患者则无法很好地区分。基于这些结果，我们推测脂质组成的变化是由 HCV 感染引起的，是由 HCV 相关的消化系统紊乱引起的，而不是疾病的进展。
