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; Amir Zarrinpar

doi:10.1038/s41467-023-40741-9

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

Nat Commun. 2023 Aug 31;14(1):5303. doi: 10.1038/s41467-023-40741-9.

Authors

Ana Carolina Dantas Machado^#¹, Stephany Flores Ramos^#^{1

2

3}, Julia M Gauglitz⁴, Anne-Marie Fassler⁵, Daniel Petras^{4

6}, Alexander A Aksenov^{4

7}, Un Bi Kim⁵, Michael Lazarowicz⁸, Abbey Barnard Giustini^{1

9

10}, Hamed Aryafar^{11

12}, Irine Vodkin¹, Curtis Warren⁵, Pieter C Dorrestein^{4

13

14

15}, Ali Zarrinpar^{16

17

18}, Amir Zarrinpar^{19

20

21

22}

Affiliations

¹ Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA, USA.
² Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
³ Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
⁴ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
⁵ Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA.
⁶ CMFI Cluster of Excellence, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
⁷ Department of Chemistry, University of Connecticut, Storrs, CT, USA.
⁸ Department of Radiology, Division of Interventional Radiology, College of Medicine, University of Florida, Gainesville, FL, USA.
⁹ Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sounds Health Care System, Seattle, WA, USA.
¹⁰ Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA.
¹¹ San Diego Imaging, San Diego, CA, USA.
¹² Departments of Radiology, University of California San Diego Medical Center, La Jolla, CA, USA.
¹³ Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA.
¹⁴ Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA.
¹⁵ Center for Computational Mass Spectrometry, University of California, San Diego, La Jolla, CA, USA.
¹⁶ Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA. ali.zarrinpar@surgery.ufl.edu.
¹⁷ Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA. ali.zarrinpar@surgery.ufl.edu.
¹⁸ J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, USA. ali.zarrinpar@surgery.ufl.edu.
¹⁹ Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA, USA. azarrinpar@ucsd.edu.
²⁰ Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA. azarrinpar@ucsd.edu.
²¹ Jennifer Moreno Department of Veterans Affairs Medical Center, La Jolla, CA, USA. azarrinpar@ucsd.edu.
²² Institute 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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Bile Acids and Salts
Hepatic Encephalopathy* / etiology
Humans
Mass Spectrometry
Portasystemic Shunt, Transjugular Intrahepatic*
Prospective Studies
Veins

Substances

Bile Acids and Salts

Abstract

Publication types

MeSH terms

Substances

Grants and funding