Altered amino acids and acylcarnitines profile in infantile intrahepatic cholestasis liver disease: implication for Traditional Chinese Medicine syndrome differentiation.

OBJECTIVE: To explore the diagnostic efficacy of blood amino acids (AAs) and acylcarnitines (ACs) profiles as metabolic biomarkers for differentiating Traditional Chinese Medicine (TCM) syndromes in infantile intrahepatic cholestatic liver disease (IICLD). METHODS: Blood samples were collected from a cohort comprising 50 healthy controls and 77 patients diagnosed with IICLD, including 43 cases categorized as cold-damp obstruction and stagnation syndrome (COS) and 34 cases as jaundice due to stasis and accumulation syndrome (JSA) based on TCM diagnostic criteria. Metabolomic analyses targeting AAs and ACs were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Compared with the healthy controls group, the IICLD group showed 23 upregulated and 2 downregulated metabolites with a screening threshold of variables of importance in projection (VIP) ≥ 1, fold change (FC) ≥ 1.2 or ≤ 0.83, and P <0.05. Six different metabolites were screened between the COS group and JSA group with a screening threshold of VIP ≥ 1, FC ≥ 1.2 or ≤ 0.83, and P <0.05. Ornithine (Orn), Decanedioy lcarnitine (C10DC), Caproylcarnitine (C6) were identified as potential biomarkers for distinguishing between the two syndromes with VIP > 2, FC ≥ 1.2 or ≤ 0.83 and P <0.05; The areas under the receiver operating characteristic curves (AUC) for these biomarkers were Orn (AUC = 0.7394), C10DC (AUC = 0.7777), and C6 (AUC = 0.686). When the levels of these three biomarkers were combined, the AUC increased to 0.922. CONCLUSION: Distinct alteration of AAs and ACs profile highlighted the oxidative stress and mitochondrial impairment in IICLD. A combined set of metabolites (Orn+ C10DC+ C6) emerged as valuable biomarker for differentiating between the COS syndrome and JSA syndromes, providing a biochemical basis for syndrome differentiation.