Clinical trial NCT06245473: Metobolomics in the Characterisation of HE
Official title: Characterization of Metabolomic Fingerprints in Patients With Hepatic Encephalopathy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatic Encephalopathy
Cirrhosis
Keywords: Hepatic encephalopathy
Cirrhosis
Metabolomics
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-02-07
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Metabolomic analysis by mass spectrometry from a 6mL blood sample of cirrhotic patients.
timeFrame: At the inclusion visit
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Sorbonne University, Pitié salpêtrière hospital
state: Ile-de-France
city: Paris
country: France
facility: Service d'hépato-gastroentérologie Hôpital Pitié Salpêtrière
Study officials:
affiliation: Sorbonne University, Pitié salpêtrière hospital
name: Marika Rudler, MD, PhD
role: STUDY_CHAIR
References: