Author information

¹Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA, USA.

²Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.

³Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.

⁴Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.

⁵Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA.

⁶CMFI Cluster of Excellence, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.

⁷Department of Chemistry, University of Connecticut, Storrs, CT, USA.

⁸Department of Radiology, Division of Interventional Radiology, College of Medicine, University of Florida, Gainesville, FL, USA.

⁹Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sounds Health Care System, Seattle, WA, USA.

¹⁰Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA.

¹¹San Diego Imaging, San Diego, CA, USA.

¹²Departments of Radiology, University of California San Diego Medical Center, La Jolla, CA, USA.

¹³Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA.

¹⁴Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA.

¹⁵Center for Computational Mass Spectrometry, University of California, San Diego, La Jolla, CA, USA.

¹⁶Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA. ali.zarrinpar@surgery.ufl.edu.

¹⁷Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA. ali.zarrinpar@surgery.ufl.edu.

¹⁸J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, USA. ali.zarrinpar@surgery.ufl.edu.

¹⁹Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA, USA. azarrinpar@ucsd.edu.

²⁰Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA. azarrinpar@ucsd.edu.

²¹Jennifer Moreno Department of Veterans Affairs Medical Center, La Jolla, CA, USA. azarrinpar@ucsd.edu.

²²Institute of Diabetes and Metabolic Health, University of California, San Diego, La Jolla, CA, USA. azarrinpar@ucsd.edu.

^#Contributed equally.

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.