Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis.
Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis.
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血浆的多变量代谢预型预测肝硬化代偿性代表的患者的存活率可预测。
DOI：
10.1016/j.jhep.2016.01.003
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发表时间：
2016-05
影响因子：
25.7
通讯作者：
Taylor-Robinson SD
中科院分区：
文献类型：
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作者：
McPhail MJW;Shawcross DL;Lewis MR;Coltart I;Want EJ;Antoniades CG;Veselkov K;Triantafyllou E;Patel V;Pop O;Gomez-Romero M;Kyriakides M;Zia R;Abeles RD;Crossey MME;Jassem W;O'Grady J;Heaton N;Auzinger G;Bernal W;Quaglia A;Coen M;Nicholson JK;Wendon JA;Holmes E;Taylor-Robinson SD
预测失代偿期肝硬化（DC）患者的生存率对肝移植的决策和资源分配具有重要意义。我们研究了高分辨率代谢谱是否可以确定与90天生存相关的代谢表型。248例受试者通过1H核磁共振（NMR）光谱和反相超高效液相色谱-飞行时间质谱联用（UPLC-TOF-MS; DC：80-衍生集，101-验证;稳定性肝硬化（CLD）20例和健康对照（HC）47例）进行血浆代谢分型。1H NMR代谢分型准确区分存活和非存活DC患者。非幸存者的NMR血浆谱归因于磷脂酰胆碱和脂质共振减少，乳酸盐、酪氨酸、甲硫氨酸和苯丙氨酸信号强度增加。这在外部验证中得到证实（受试者工作曲线下面积[AUROC] = 0.96（95% CI 0.90-1.00，灵敏度98%，特异性89%）。UPLC-TOF-MS证实，溶血磷脂酰胆碱和磷脂酰胆碱[LPC/PC]在非存活者中下调（UPLC-TOF-MS曲线AUROC为0.94（95% CI 0.89-0.98，灵敏度100%，特异性85% [正离子检测]）。LPC浓度与DC中细胞死亡的循环标志物（M30和M65）水平呈负相关。与对照组相比，DC患者的肝组织的组织学检查证实肝细胞死亡增加。肝移植时交叉肝取样表明，肝内皮床是DC中循环总细胞角蛋白-18增加的来源。血浆代谢分型准确预测DC的死亡率。LPC和氨基酸失调与反映肝细胞死亡的死亡率和疾病严重程度增加相关。
Predicting survival in decompensated cirrhosis (DC) is important in decision making for liver transplantation and resource allocation. We investigated whether high-resolution metabolic profiling can determine a metabolic phenotype associated with 90-day survival. Two hundred and forty-eight subjects underwent plasma metabotyping by 1H nuclear magnetic resonance (NMR) spectroscopy and reversed-phase ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS; DC: 80-derivation set, 101-validation; stable cirrhosis (CLD) 20 and 47 healthy controls (HC)). 1H NMR metabotyping accurately discriminated between surviving and non-surviving patients with DC. The NMR plasma profiles of non-survivors were attributed to reduced phosphatidylcholines and lipid resonances, with increased lactate, tyrosine, methionine and phenylalanine signal intensities. This was confirmed on external validation (area under the receiver operating curve [AUROC] = 0.96 (95% CI 0.90–1.00, sensitivity 98%, specificity 89%). UPLC-TOF-MS confirmed that lysophosphatidylcholines and phosphatidylcholines [LPC/PC] were downregulated in non-survivors (UPLC-TOF-MS profiles AUROC of 0.94 (95% CI 0.89–0.98, sensitivity 100%, specificity 85% [positive ion detection])). LPC concentrations negatively correlated with circulating markers of cell death (M30 and M65) levels in DC. Histological examination of liver tissue from DC patients confirmed increased hepatocyte cell death compared to controls. Cross liver sampling at time of liver transplantation demonstrated that hepatic endothelial beds are a source of increased circulating total cytokeratin-18 in DC. Plasma metabotyping accurately predicts mortality in DC. LPC and amino acid dysregulation is associated with increased mortality and severity of disease reflecting hepatocyte cell death.