Metabolic Characterization of Advanced Liver Fibrosis in HCV Patients as Studied by Serum 1H-NMR Spectroscopy.
Metabolic Characterization of Advanced Liver Fibrosis in HCV Patients as Studied by Serum 1H-NMR Spectroscopy.
复制标题
DOI：
10.1371/journal.pone.0155094
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Millet O
中科院分区：
文献类型：
--
作者：
Embade N;Mariño Z;Diercks T;Cano A;Lens S;Cabrera D;Navasa M;Falcón-Pérez JM;Caballería J;Castro A;Bosch J;Mato JM;Millet O
几种病因导致慢性肝病，包括慢性丙型肝炎病毒感染（HCV）。尽管肝病的发病率很高，经济和医疗后果严重，但由于缺乏有效的非侵入性诊断方法，肝病仍然经常被忽视。虽然已经测试了几种用于检测纤维化的技术，但可用的生物标志物仍然存在严重的限制，这妨碍了它们在临床诊断中的使用。肝脏疾病也一直是代谢组学分析的主题。在这里，我们证明了1H NMR光谱表征HCV诱导的肝纤维化的代谢的适用性。无纤维化或肝硬化的HCV患者的血清样品通过NMR光谱分析，并将结果提交给多变量和单变量统计分析。PLS-DA测试能够区分晚期纤维化和非纤维化患者，并且发现几种代谢物在肝硬化患者中上调或下调。通过ROC分析验证了最显著调节的代谢物的适用性。我们的研究表明，胆碱、乙酰乙酸和低密度脂蛋白是预测丙型肝炎患者肝硬化的最具信息性的生物标志物。我们的研究结果表明，1H-NMR光谱的统计分析是能够区分纤维化和非纤维化患者患有HCV，代表一种新的诊断应用NMR光谱。
Several etiologies result in chronic liver diseases including chronic hepatitis C virus infection (HCV). Despite its high incidence and the severe economic and medical consequences, liver disease is still commonly overlooked due to the lack of efficient non-invasive diagnostic methods. While several techniques have been tested for the detection of fibrosis, the available biomarkers still present severe limitations that preclude their use in clinical diagnostics. Liver diseases have also been the subject of metabolomic analysis. Here, we demonstrate the suitability of 1H NMR spectroscopy for characterizing the metabolism of liver fibrosis induced by HCV. Serum samples from HCV patients without fibrosis or with liver cirrhosis were analyzed by NMR spectroscopy and the results were submitted to multivariate and univariate statistical analysis. PLS-DA test was able to discriminate between advanced fibrotic and non-fibrotic patients and several metabolites were found to be up or downregulated in patients with cirrhosis. The suitability of the most significantly regulated metabolites was validated by ROC analysis. Our study reveals that choline, acetoacetate and low-density lipoproteins are the most informative biomarkers for predicting cirrhosis in HCV patients. Our results demonstrate that statistical analysis of 1H-NMR spectra is able to distinguish between fibrotic and non-fibrotic patients suffering from HCV, representing a novel diagnostic application for NMR spectroscopy.