Abstract
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.
Highlights
The clinical manifestations of Human cytomegalovirus (HCMV)-induced liver injury are diverse, making clinical diagnosis difficult
We divided the patients into three subgroups based on their clinical manifestations and identified 29 differential metabolites involved in a variety of amino acid, fatty acid and energy metabolism disorders
The increase in glutamine and glutamate metabolism during HCMV infection was previously demonstrated in a series of in vitro experiments[20,23,24]
Summary
The clinical manifestations of HCMV-induced liver injury are diverse, making clinical diagnosis difficult. The clinical presentations of EHBA and infantile cholestatic hepatopathy (ICH) are similar. In both conditions, jaundice, hypopigmented stools, dark urine and hepatosplenomegaly develop within the first 3 month of life. New techniques are needed for the differential diagnosis of ICH and EHBA, and the mechanisms by which HCMV causes different types of liver injury should be determined. A series of cell metabolomic studies have evaluated the changes in cellular metabolism caused by HCMV infection, which involve the metabolism of glucose and glutamine[19,20,21,22]. We analyzed the endogenous metabolites in plasma samples from infants with HCMV-induced liver injury using untargeted gas chromatography-mass spectrometry (GC-MS). Orthogonal partial least squares-discriminate analysis (OPLS-DA) was applied to analyse the differences between HCMV infantile hepatitis (IH), HCMV ICH, HCMV EHBA and normal control (NC) subjects
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