Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China.
J Pharm Biomed Anal. 2021 May 10;198:114004. doi: 10.1016/j.jpba.2021.114004. Epub 2021 Mar 6.
Prevalence of acute-on-chronic liver failure (ACLF) patients is growing worldwide, associating with multi-organ failure and high short-term mortality rates. ACLF can be of varying entity manifestation, whereas it remains poorly defined. Traditional Chinese medicine (TCM) stratifies ACLF into two types, damp hot (DH) and cold damp (CD), by seasoned TCM practitioners, for specific treatment with different TCMs. The biggest challenge for the outcome of TCM therapy is the accuracy of diagnosis. However, it is difficult to guarantee it due to lack of the molecule classification of ACLF. Herein, we recruited 58 subjects including 34 ACLF patients (18 DH and 16 CD) and 24 healthy controls, and analyzed serum metabolic profiles using untargeted ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics approach. A total of 10 serum metabolites were found as potential biomarkers for diagnosis of ACLF. Among them, taurochenodesoxycholic acid (N3), glycyldeoxycholic acid (N5) and 12-HETE-GABA (N7), varied between two types of ACLF and can be merged as a combination marker to differentiate CD from DH patients with area under the receiver operating curve (AUC) of 0.928 (95 % CI 0.8-1). CD patients possessed comparatively higher bile acid metabolism and lower arachidonic acid metabolism compared with DH patients. The results provide not only serum molecules for early accurate diagnosis of ACLF patients, but also potential clinical biomarkers for classification of CD and DH types. The findings clarify that molecular markers will be objective criteria for diagnosis of clinical types in TCM practice.
全球范围内，慢性肝衰竭（ACLF）患者的发病率不断上升，与多器官衰竭和高短期死亡率相关。ACLF 可能具有不同的实体表现，但目前仍未明确界定。传统中医（TCM）根据有经验的中医将 ACLF 分为湿热（DH）和寒湿（CD）两种类型，采用不同的 TCM 进行针对性治疗。TCM 治疗效果的最大挑战是诊断的准确性。然而，由于 ACLF 缺乏分子分类，因此很难保证其准确性。在此，我们招募了 58 名受试者，包括 34 名 ACLF 患者（18 名 DH 和 16 名 CD）和 24 名健康对照者，并使用非靶向超高效液相色谱-四极杆飞行时间质谱联用（UPLC-Q-TOF/MS）代谢组学方法分析血清代谢谱。共发现 10 种血清代谢物可作为 ACLF 诊断的潜在生物标志物。其中，牛磺去氧胆酸（N3）、甘氨去氧胆酸（N5）和 12-HETE-GABA（N7）在两种 ACLF 类型之间存在差异，可合并为组合标志物，用于区分 CD 和 DH 患者，其曲线下面积（AUC）为 0.928（95%CI 0.8-1）。与 DH 患者相比，CD 患者的胆汁酸代谢较高，花生四烯酸代谢较低。这些结果不仅为 ACLF 患者的早期准确诊断提供了血清分子，还为 CD 和 DH 型的分类提供了潜在的临床生物标志物。研究结果表明，分子标志物将成为 TCM 实践中临床分型的客观标准。
