HP06 - Untargeted Profiling of Serum Metabolites in Dogs with Chronic Hepatitis

Abstract: Background – Definitive diagnosis of chronic hepatitis (CH) in dogs requires histopathological assessment. Non-invasive biomarkers of CH would be beneficial. Metabolomics facilitates the description of disease pathophysiology, progression, and therapeutic response at the metabolic level.Objective – Describe differences in the serum metabolomic profiles of dogs with CH in comparison to healthy control (HC) dogs and dogs with chronic enteropathy (CE).Animals – Serum samples from 16 dogs with CH, 16 dogs with CE, and 16 HC dogs.Methods – Retrospective cross-sectional study. Untargeted metabolomic analysis was performed by ultra-high performance liquid chromatography/tandem accurate mass spectrometry. Univariate analyses among CH, CE, and HC dogs were performed using Kruskal-Wallis tests. P-values were adjusted for multiple comparisons. Significance was set at q <.05. Results – A total of 140 out of 959 metabolites were significantly different among groups. Twenty-six metabolites were uniquely increased in the CH group. The most remarkable peak intensities included: aromatic amino acids (phenylalanine [q=.008]), organic acids (formiminoglutamate [q=.003]), phospholipids (sphinganine 1-phosphate [q=.002]), cofactors (quinolinate [q=.02]), peptides (gamma glutamylphenylalanine [q=.001]), and nucleotides (3-ureidoisobutyrate [q=.0002]). Principal component analysis and heat dendrograms revealed distinctive clustering and metabolomic profiles among the three groups.Conclusions and clinical importance – Dogs with CH have a distinct serum metabolite profile compared to dogs with CE or HC dogs. Targeted assessment of these differentially expressed metabolites is necessary to confirm this and to determine their clinical utility.