Serum metabolic signatures of primary biliary cirrhosis and primary sclerosing cholangitis.
Serum metabolic signatures of primary biliary cirrhosis and primary sclerosing cholangitis.
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DOI：
10.1111/liv.12680
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Chalasani N
中科院分区：
文献类型：
--
作者：
Bell LN;Wulff J;Comerford M;Vuppalanchi R;Chalasani N
更深入地了解胆汁淤积性疾病是必要的，以推进诊断工具和治疗方案的条件，如原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）。本研究的目的是确定和比较PBC（n=18）或PSC（n=21）患者和健康对照（n=10）的血清代谢组，并鉴定可能区分这两种胆汁淤积性疾病的代谢物。使用基于质谱的非靶向生化分析方法，我们鉴定了420种血清代谢物，其中101种在PBC组和对照组之间存在显著差异（p≤0.05），115种在PSC组和对照组之间存在显著差异，56种在PSC组和PBC组之间存在显著差异。随机森林分类分析能够以95%的准确度区分PBC或PSC患者，所选生化物质反映蛋白质和氨基酸代谢被确定为主要贡献者。与胆汁酸代谢、脂质代谢、炎症和氧化应激/脂质过氧化相关的代谢也被确定为在比较疾病组和对照组时显著不同，其中一些途径在PBC和PSC组中受到不同的影响。在这项研究中，确定了与胆汁淤积性疾病相关的新的代谢变化，这些变化在PBC和PSC之间既一致又不同。需要在更大的患者队列中进行验证研究，以确定这些生化标志物对PBC和PSC患者的诊断和治疗监测的效用。
A greater understanding of cholestatic disease is necessary to advance diagnostic tools and therapeutic options for conditions such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The purpose of this study was to determine and compare the serum metabolomes of patients with PBC (n=18) or PSC (n=21) and healthy controls (n=10) and to identify metabolites that may differentiate these two cholestatic diseases. Using a mass spectrometry-based, non-targeted biochemical profiling approach we identified 420 serum metabolites, 101 that differed significantly (p≤0.05) between PBC and control groups, 115 that differed significantly between PSC and control groups, and 56 that differed significantly between PSC and PBC groups. Random forest classification analysis was able to distinguish patients with PBC or PSC with 95% accuracy with selected biochemicals reflective of protein and amino acid metabolism identified as the major contributors. Metabolites related to bile acid metabolism, lipid metabolism, inflammation, and oxidative stress/lipid peroxidation were also identified as differing significantly when comparing the disease groups and controls, with some of these pathways differentially affected in the PBC and PSC groups. In this study identified novel metabolic changes associated with cholestatic disease that were both consistent and different between PBC and PSC. Validation studies in larger patient cohorts are required to determine the utility of these biochemical markers for diagnosis and therapeutic monitoring of patients with PBC and PSC.
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影响因子：
5.1
作者：
Kowdley, K V
通讯作者：
Kowdley, K V
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29.4
作者：
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作者：
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通讯作者：
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