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

Nature Communications (Aug 2023)

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

Affiliations

Ana Carolina Dantas Machado: Division of Gastroenterology and Hepatology, University of California, San Diego
Stephany Flores Ramos: Division of Gastroenterology and Hepatology, University of California, San Diego
Julia M. Gauglitz: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego
Anne-Marie Fassler: Department of Surgery, College of Medicine, University of Florida
Daniel Petras: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego
Alexander A. Aksenov: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego
Un Bi Kim: Department of Surgery, College of Medicine, University of Florida
Michael Lazarowicz: Department of Radiology, Division of Interventional Radiology, College of Medicine, University of Florida
Abbey Barnard Giustini: Division of Gastroenterology and Hepatology, University of California, San Diego
Hamed Aryafar: San Diego Imaging
Irine Vodkin: Division of Gastroenterology and Hepatology, University of California, San Diego
Curtis Warren: Department of Surgery, College of Medicine, University of Florida
Pieter C. Dorrestein: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego
Ali Zarrinpar: Department of Surgery, College of Medicine, University of Florida
Amir Zarrinpar: Division of Gastroenterology and Hepatology, University of California, San Diego

DOI: https://doi.org/10.1038/s41467-023-40741-9
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 14

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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