Portosystemic shunt placement reveals blood signatures for the development of hepatic encephalopathy through mass spectrometry

Ana Carolina Dantas Machado, Stephany Flores Ramos, Julia M. Gauglitz, Anne-Marie Fassler, Daniel Petras, Alexander A. Aksenov, Un Bi Kim, Michael Lazarowicz, Abbey Barnard Giustini, Hamed Aryafar, Irine Vodkin, Curtis Warren, Pieter C. Dorrestein, Ali Zarrinpar () and Amir Zarrinpar ()
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Ana Carolina Dantas Machado: University of California, San Diego
Stephany Flores Ramos: University of California, San Diego
Julia M. Gauglitz: University of California, San Diego
Anne-Marie Fassler: University of Florida
Daniel Petras: University of California, San Diego
Alexander A. Aksenov: University of California, San Diego
Un Bi Kim: University of Florida
Michael Lazarowicz: University of Florida
Abbey Barnard Giustini: University of California, San Diego
Hamed Aryafar: San Diego Imaging
Irine Vodkin: University of California, San Diego
Curtis Warren: University of Florida
Pieter C. Dorrestein: University of California, San Diego
Ali Zarrinpar: University of Florida
Amir Zarrinpar: University of California, San Diego

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Elective transjugular intrahepatic portosystemic shunt (TIPS) placement can worsen cognitive dysfunction in hepatic encephalopathy (HE) patients due to toxins, including possible microbial metabolites, entering the systemic circulation. We conducted untargeted metabolomics on a prospective cohort of 22 patients with cirrhosis undergoing elective TIPS placement and followed them up to one year post TIPS for HE development. Here we suggest that pre-existing intrahepatic shunting predicts HE severity post-TIPS. Bile acid levels decrease in the peripheral vein post-TIPS, and the abundances of three specific conjugated di- and tri-hydroxylated bile acids are inversely correlated with HE grade. Bilirubins and glycerophosphocholines undergo chemical modifications pre- to post-TIPS and based on HE grade. Our results suggest that TIPS-induced metabolome changes can impact HE development, and that pre-existing intrahepatic shunting could be used to predict HE severity post-TIPS.

Date: 2023
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DOI: 10.1038/s41467-023-40741-9

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