Effect of the transjugular intrahepatic portosystemic shunt on peptidomics composition of peripheral plasma

Abstract Background & Aims Portal hypertension often develops in patients with advanced chronic liver diseases (CLD), especially cirrhosis and is associated with complications of the disease, such as gastrointestinal bleeding and ascites, which account for high mortality rates. The transjugular intrahepatic portosystemic shunt (TIPS) is one of only a few treatment options for portal hypertension aiming at the decrease of portal venous pressure by establishing an artificial passage for blood from the gastrointestinal tract directly to the liver vein. The current study aimed to investigate the molecular composition of plasma samples from patients with portal hypertension to characterize mediators influenced by TIPS intervention and involved in gut-liver crosstalk. Methods The plasma of 23 patients suffering from advanced CLD with portal hypertension was collected from peripheral veins before and after TIPS treatment and was analyzed by liquid chromatography-mass spectrometry (LC-MS) using a non-targeted approach. Substances in the molecular range of 100 to 1,500 (m/z) with concentration differences induced by the TIPS intervention were identified in peripheral blood. The identified mediators were sequenced through MS/MS and analyzed through literature mining to gain an insight into their function. Results Overall, eleven low molecular weight mediators revealed concentration changes triggered by the TIPS intervention. From these, four peptides and six metabolites were significantly decreased after TIPS, whereas one metabolite showed an increase after the medical procedure. Conclusions In conclusion, we identified in this study ten new biomarker candidates for portal hypertension in patients with CLD, with potential involvement in the regulation of pathological gut-liver crosstalk.