Background The canonical pathogenesis of hepatic encephalopathy (HE) in liver cirrhosis pivots on amino acid metabolism. HE is subsequent to transjugular intrahepatic portosystemic shunt (TIPS), distinct from the common HE in liver cirrhosis, and the metabolism of post-TIPS HE is not fully understood. The aim of this study was to investigate the metabolic profile of pre-TIPS metabolomics and to determine the most altered pre-TIPS metabolites to alert the onset of post-TIPS HE.

Methods Ten serum samples, each from patients with and without overt HE within 6 months after TIPS, were chosen by randomized sampling in an ongoing cohort study (ChiCTR2000039616). Untargeted metabolomics and targeted lipidomics analyses were performed based on ultrahigh-performance liquid chromatography-tandem mass spectrometry.

Results There were no significant differences in the baseline characteristics between the two groups after randomized sampling. In the untargeted metabolomics analysis, 46 (0.08%) out of 1255 metabolites were significantly associated with post-TIPS HE, of which 12 and 34 metabolites were up-regulated and down-regulated in the post-TIPS HE, respectively. These metabolites are tightly related to the alanine, aspartate and glutamate metabolism, fatty acid biosynthesis, and glyceropholipid metabolism pathways. Intriguingly, of 46, 14 (30.4%) differential metabolites came from the lysophosphatide family, which were mainly down-regulated in post-TIPS HE. Further targeted lipidomics identified 44 (7.8%) differential lipids out of 564 lipid metabolites. Of the 15 up-regulated lipid metabolites in the post-TIPS HE group, 12 (80%) were triacylglycerols. In contrast, there were 17 (58.6%) phospholipids and 9 (31%) lysophosphatides out of 29 down-regulated lipid metabolites in post-TIPS HE.

Conclusions Lipid metabolism disturbances, features as up-regulated triacylglycerols and down-regulated glycerophospholipds, are associated with the onset of post-TIPS HE in liver cirrhosis.