Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Pediatrics, Nanjing, 210023, China.
Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatics, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Sci Rep. 2017 Nov 16;7(1):15696. doi: 10.1038/s41598-017-16051-8.
Human cytomegalovirus (HCMV) infection in infants is a global problem and the liver is a target organ of HCMV invasion. However, the mechanism by which HCMV causes different types of liver injury is unclear, and there are many difficulties in the differential diagnosis of HCMV infantile cholestatic hepatopathy (ICH) and extrahepatic biliary atresia (EHBA). We established a non-targeted gas chromatography-mass spectrometry metabolomics method in conjunction with orthogonal partial least squares-discriminate analysis based on 127 plasma samples from healthy controls, and patients with HCMV infantile hepatitis, HCMV ICH, and HCMV EHBA to explore the metabolite profile of different types of HCMV-induced liver injury. Twenty-nine metabolites related to multiple amino acid metabolism disorder, nitrogen metabolism and energy metabolism were identified. Carbamic acid, glutamate, L-aspartic acid, L-homoserine, and noradrenaline for HCMV ICH vs. HCMV EHBA were screened as potential biomarkers and showed excellent discriminant performance. These results not only revealed the potential pathogenesis of HCMV-induced liver injury, but also provided a feasible diagnostic tool for distinguishing EHBA from ICH.
人巨细胞病毒(HCMV)感染在婴儿中是一个全球性问题,肝脏是 HCMV 侵袭的靶器官。然而,HCMV 导致不同类型肝损伤的机制尚不清楚,HCMV 婴儿胆汁淤积性肝炎(ICH)和肝外胆管闭锁(EHBA)的鉴别诊断存在许多困难。我们建立了一种非靶向气相色谱-质谱代谢组学方法,结合正交偏最小二乘判别分析,基于 127 例健康对照者和 HCMV 婴儿肝炎、HCMV ICH 和 HCMV EHBA 患者的血浆样本,探讨不同类型 HCMV 引起的肝损伤的代谢谱。鉴定出 29 种与多种氨基酸代谢紊乱、氮代谢和能量代谢相关的代谢物。对 HCMV ICH 与 HCMV EHBA 相比,筛选出氨基甲酰酸、谷氨酸、L-天冬氨酸、L-高丝氨酸和去甲肾上腺素作为潜在的生物标志物,具有出色的判别性能。这些结果不仅揭示了 HCMV 引起肝损伤的潜在发病机制,而且为鉴别 EHBA 与 ICH 提供了一种可行的诊断工具。