McPhail Mark J W, Montagnese Sara, Villanova Manuela, El Hadi Hamza, Amodio Piero, Crossey Mary M E, Williams Roger, Cox I Jane, Taylor-Robinson Simon D
Liver Unit, Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, London, W2 1NY, UK.
Department of Medicine DIMED, University of Padova, Padova, Italy.
Metab Brain Dis. 2017 Apr;32(2):331-341. doi: 10.1007/s11011-016-9904-0. Epub 2016 Sep 17.
To date urinary metabolic profiling has been applied to define a specific metabolic fingerprint of hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of other complications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinary proton nuclear magnetic resonance (H-NMR) spectra were acquired and NMR data from 52 patients with cirrhosis (35 male; 17 female, median (range) age [60 (18-81) years]) and 17 controls were compared. A sub-set of 45 patients (33 male; 12 female, [60 (18-90) years, median model for end stage liver disease (MELD) score 11 (7-27)]) were fully characterised by West-Haven criteria, Psychometric Hepatic Encephalopathy Score (PHES) and electroencephalogram (EEG), and defined as overt HE (OHE, n = 21), covert HE (cHE, n = 7) or no HE (n = 17). Urinary proton nuclear magnetic resonance (H-NMR) spectra were analysed by partial-least-squares discriminant analysis (PLS-DA). The results showed good discrimination between patients with cirrhosis (n = 52) and healthy controls (n = 17) (R2X = 0.66, R2Y = 0.47, Q2Y = 0.31, sensitivity-60 %, specificity-100 %) as the cirrhosis group had higher 1-methylnicotinamide with lower hippurate, acetate, phenylacetylglycine and N-methyl nicotinic acid levels. While patients with OHE could be discriminated from those with no HE, with higher histidine, citrate and creatinine levels, the best models lack robust validity (R2X = 0.65, R2Y = 0.48, Q2Y = 0.12, sensitivity-100 %, specificity-64 %) with the sample size used. Urinary H-NMR metabolic profiling did not discriminate patients with cHE from those without HE, nor discriminate subjects on the basis of PHES/EEG result or MELD score. In conclusion, patients with cirrhosis showed different urinary H-NMR metabolic profiles compared to healthy controls and those with OHE may be distinguished from those with no HE although larger studies are required. However, urinary H-NMR metabolic profiling did not discriminate patients with differing grades of HE or according to severity of underlying liver disease.
迄今为止，尿代谢谱分析已被用于在肝硬化背景下定义肝细胞癌的特定代谢指纹图谱。其在肝硬化其他并发症（如肝性脑病（HE））分层中的作用仍有待确定。采集了52例肝硬化患者（35例男性；17例女性，年龄中位数（范围）[60（18 - 81）岁]）和17例对照的尿质子核磁共振（H-NMR）谱，并对NMR数据进行了比较。45例患者（33例男性；12例女性，[60（18 - 90）岁，终末期肝病模型（MELD）评分中位数11（7 - 27）]）的亚组通过韦斯特-黑文标准、心理测量肝性脑病评分（PHES）和脑电图（EEG）进行了全面表征，并被定义为显性HE（OHE，n = 21）、隐性HE（cHE，n = 7）或无HE（n = 17）。通过偏最小二乘判别分析（PLS-DA）对尿质子核磁共振（H-NMR）谱进行分析。结果显示，肝硬化患者（n = 52）与健康对照（n = 17）之间有良好的区分度（R2X = 0.66，R2Y = 0.47，Q2Y = 0.31，敏感性 - 60%，特异性 - 100%），因为肝硬化组的1-甲基烟酰胺含量较高，而马尿酸盐、乙酸盐、苯乙酰甘氨酸和N-甲基烟酸水平较低。虽然OHE患者可以与无HE患者区分开来，其组氨酸、柠檬酸盐和肌酐水平较高，但使用的样本量下，最佳模型缺乏稳健的有效性（R2X = 0.65，R2Y = 0.48，Q2Y = 0.12，敏感性 - 100%，特异性 - 64%）。尿H-NMR代谢谱分析无法区分cHE患者与无HE患者，也无法根据PHES/EEG结果或MELD评分区分受试者。总之，与健康对照相比，肝硬化患者显示出不同的尿H-NMR代谢谱，虽然需要更大规模的研究，但OHE患者可能与无HE患者区分开来。然而，尿H-NMR代谢谱分析无法区分不同等级HE患者或根据潜在肝病严重程度进行区分。
