Metobolomics in the Characterisation of HE (METABO-EH)

Characterization of Metabolomic Fingerprints in Patients With Hepatic Encephalopathy

Hepatic encephalopathy is (HE) defined by the neurological and/or neuropsychological symptoms caused by an acute or chronic liver disease and/or a portosystemic shunt. Its pathophysiology is still debated, although the synergic role of hyperammonemia and inflammation is now admitted for years. Several additional mechanisms have been suspected, one of them being an altered permeability of the brain blood barrier (BBB). Nevertheless, many aspects remain poorly understood.

The rise of "-omics" techniques, and especially metabolomics, allowed to identify more precisely the different metabolic pathways that are involved in the pathophysiology of HE. Using a high flow chemistry technique and multivariate data analysis, metabolomics is an accurate way to understand the pathophysiology and pathogenesis of multifactorial diseases such as HE. Several studies have been published in cirrhosis. It has been suggested that serum metabolites at admission, as well as thyroxine, can predict advanced HE in patients without brain failure. In a cohort including more than 600 patients, a higher microbially-derived metabolites, together with a lower thyroxine level, were associated with further development of brain failure. In another study from the same team, serum and urinary metabolites were significantly different in hospitalised patients who had developed poor outcome or not. Another study conducted in the CANONIC cohort as also found changes in metabolites of patients with cirrhosis and acute-on-chronic liver failure (ACLF), revealing mitochondrial dysfunction in peripheral organs that may contribute to organ failures. Last, our team previously analysed plasma and cerebrospinal fluid (CSF) samples of patients with cirrhosis and HE hospitalised in intensive care unit (ICU), showing alteration in ammonia and amino-acids metabolism, and also in energy metabolism. However, in the latest study, ALCF grading was not available. As many of these patients were in a severe condition, one could hypothesize that the metabolomic changes observed in these patients may have been confounded by an ACLF profile. Therefore, the objective of this study is to characterize the metabolomic fingerprints of HE in patients with cirrhosis, using 4 different groups of patients: patients with or without HE, with or without ALCF.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy; Cirrhosis
• Intervention / Treatment: Diagnostic test: blood sample

• Study Type: Observational
• Enrollment (Actual): 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Service d'hépato-gastroentérologie Hôpital Pitié Salpêtrière
  • Ile-de-France
    • Paris, Ile-de-France, France, 75013
      • Sorbonne University, Pitié salpêtrière hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients over 18 years of age with cirrhosis according to the presence of ACLF or hepatic encephalopathy or not.

Description

Inclusion Criteria:

• Patient aged ≥ 18 years
• Patient with cirrhosis of any etiology
• Informed patient who does not object to participating in the study
• Patient affiliated to a social security scheme or entitled beneficiary

Exclusion Criteria:

• Pregnant or breast-feeding women
• Protected populations: under guardianship or trusteeship
• Previous liver transplant
• Patient on AME

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Metabolomic analysis by mass spectrometry from a 6mL blood sample of cirrhotic patients.	At the inclusion visit

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Marika Rudler, MD, PhD, Sorbonne University, Pitié salpêtrière hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2024
• Primary Completion (Actual): April 23, 2024
• Study Completion (Actual): April 23, 2024

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Metabolomics; Cirrhosis; Hepatic encephalopathy
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Brain Diseases, Metabolic; Liver Failure; Hepatic Insufficiency; Fibrosis; Brain Diseases; Hepatic Encephalopathy
• Other Study ID Numbers: APHP220279

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No