Background and Objective:Transjugular intrahepatic portal shunt (TIPS) insertion could promote weight gain and muscle and fat mass increase in patients with cirrhosis. However, few studies have focused on metabolic changes after TIPS. This study aims to explore metabolic changes after TIPS and potential biomarkers of adverse events.Methods:Peripheral and portal serum samples were collected before and after TIPS insertion. Untargeted metabolomics was performed using ultra-high-performance liquid chromatography-mass spectrometry. Spearman’s correlation analysis was used to determine the relationship between metabolites and clinical parameters. Metabolite set enrichment analysis was performed to explore enriched pathways. The predictive value of the metabolites was calculated by receiver operating characteristic curve (ROC) analysis.Results:Metabolites in the peripheral and portal serum significantly changed early after TIPS. Some lipid metabolites were significantly correlated with liver function parameters. Both elevated and depleted metabolites were mainly enriched in amino acid metabolism. Nine and 12 portal metabolites have moderate predictive value in post-TIPS liver function decline and hepatic encephalopathy (HE), separately (area under curve >0.7).Conclusion:Metabolites in the peripheral and portal veins significantly changed after TIPS. Some metabolic changes might be ascribed to liver function decline early after TIPS. Nine and 12 portal metabolites might be potential biomarkers in prediction of liver function decline and HE, separately.