Arthur G. Zupko Institute for Systems Pharmacology and Pharmacogenomics, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, NY 11201, USA.
Hepatology, Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland.
Molecules. 2022 Jun 20;27(12):3935. doi: 10.3390/molecules27123935.
Ascites is a common complication of decompensated liver cirrhosis, and yet relatively little is known about its biochemical composition. We conducted two metabolomic investigations, comparing the profile of ascites from 33 cirrhotic patients and postoperative peritoneal drainage fluid from 33 surgical patients (Experiment 1). The profile of paired ascites and plasma was also compared in 17 cirrhotic patients (Experiment 2). Gas chromatography−mass spectrometry-based metabolomics identified 29 metabolites that significantly characterized ascites fluid, whether postoperative drainage fluid or plasma were used as controls. Ten elevated amino acids (glutamine, proline, histidine, tyrosine, glycine, valine, threonine, methionine, lysine, phenylalanine) and seven diminished lipids (laurate, myristate, palmitate, oleate, vaccenate, stearate, cholesterol) largely comprised the cirrhotic ascites metabolomic phenotype that differed significantly (adjusted p < 0.002 to 0.03) from peritoneal drainage fluid or plasma. The pattern of upregulated amino acids in cirrhotic ascites did not indicate albumin proteolysis by peritoneal bacteria. Bidirectional clustering showed that the more severe the cirrhosis, the lower the lipid concentration in ascitic fluid. The metabolomic compartment of ascites in patients with decompensated cirrhosis is characterized by increased amino acids and decreased lipids. These novel findings have potential relevance for diagnostic purposes.
腹水是失代偿性肝硬化的常见并发症,但对其生化成分的了解相对较少。我们进行了两项代谢组学研究,比较了 33 例肝硬化患者的腹水和 33 例手术患者术后腹腔引流液的特征(实验 1)。还比较了 17 例肝硬化患者配对腹水和血浆的特征(实验 2)。基于气相色谱-质谱的代谢组学鉴定出 29 种代谢物,这些代谢物显著特征化了腹水液,无论术后引流液还是血浆作为对照。10 种升高的氨基酸(谷氨酰胺、脯氨酸、组氨酸、酪氨酸、甘氨酸、缬氨酸、苏氨酸、蛋氨酸、赖氨酸、苯丙氨酸)和 7 种减少的脂质(月桂酸、肉豆蔻酸、棕榈酸、油酸、蓖麻酸、硬脂酸、胆固醇)主要构成了与术后腹腔引流液或血浆显著不同(调整后的 p 值<0.002 至 0.03)的肝硬化腹水代谢组学特征。肝硬化腹水中上调氨基酸的模式并未表明腹膜细菌对白蛋白的蛋白水解作用。双向聚类显示,肝硬化越严重,腹水脂质浓度越低。失代偿性肝硬化患者腹水的代谢组学特征是氨基酸增加和脂质减少。这些新发现对诊断目的具有潜在意义。