Characterization of Metabolomic Fingerprints in Patients With Acute Liver Failure and Acute-on-chronic Liver Failure With Hepatic Encephalopathy

NCT05772585 | Withdrawn

• 1 other identifier: APHP221332
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Hepatic encephalopathy is a frequent complication of both acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) and could be responsible among other neurological complications of residual impairment after liver transplantation. Specific metabolomic studies have shed light into pathophysiology. Nevertheless, whether HE metabolomic fingerprints differ between HE in ALF and HE in ACLF and their evolution after liver transplantation (LT) is unknown. The aim of our study is to analyse the metabolomic fingerprint in plasma of 2 different groups of patients before and after LT:

• hospitalized patients with ALF and HE
• hospitalized patients with ACLF and HE We will analyse metabolomic results to explore if there is any difference in metabolomic fingerprints between these 2 groups and if LT modify the metabolomic fingerprint in plasma in these 2 groups and in the same way. We will collect blood samples in these 2 groups on the day of HE occurring and then on day 1, day 7 and day 30 (+/- 2 days) after LT. We aim to enroll 10 patients in ALF group and 20 patients in ACLF group. Inclusion criteria are defined as age \> 18 years, patient presenting with ALF (Synthetic liver failure (INR \> 1.5) with hepatic encephalopathy (grade 1-4 of West-Haven classification), without pre-existing hepatopathy, HE beginning within \<26 weeks) or ACLF (≥ grade 1 from CANONIC criteria), and clinical HE (grade 1-4 of West-Haven classification) on the day of enrolment. Exclusion criteria are defined as age \< 18 years, absence of HE, LT without pre-existing HE, patients who already undergone a LT, legally protected person. An EDTA blood sample will be collected, centrifuged and frozen on the day of enrolment, then on day 1, day 7 and day 30 (+/- 2 days) after LT. Metabolomic analyses will be performed by different techniques but especially with high resolution liquid phase mass spectrometry in collaboration with CEA. Statistical analyses will be both univariate (Mann-Whitney or Wilcoxon tests) and multivariate (with a classical and adapted method for metabolomic studies: Partial Least-Squares Discriminant Analysis (PLS-DA)). We expect to identify different metabolomic fingerprints between HE in both ALF and ACLF patients as well as different kinetics for symptoms resolution after LT. The long-term objective is to target the specific metabolic pathways for each group in order to allow development of new targeted drugs against HE in these 2 different conditions.

Conditions

Hepatic Encephalopathy; Acute Liver Failure; Acute on Chronic Liver Failure

Keywords

Hepatic Encephalopathy; Acute liver failure; Acute on chronic liver failure; Liver transplantation; Metabolomics

Outcome Measures

Primary Outcomes (1)

• comparison of metabolomic fingerprints of hepatic encephalopathy between ALF and ACLF

  Partial Least-Squares Discriminant Analysis (PLS-DA).

  6 months

Study Arms (1)

patients ALF and ACLF

patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) with hepatic encephalopathy

Other: Blood collection

Interventions

Blood collection OTHER

Blood collection (1 to 4 times for each patient) in order to perform metabolomic analyses of the plasmatic fingerprints of patients with hepatic encephalopathy

Also known as: Metabolomics analyses, High resolution liquid phase mass spectrometry

patients ALF and ACLF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients hospitalised for acute or acute-on-chronic liver failure, with hepatic encephalopathy and receiving a liver transplant following medical progression

You may qualify if:

• age \> 18 years
• patient presenting with:
• ALF (Synthetic liver failure (INR \> 1.5) with hepatic encephalopathy (grade 1-4 of West-Haven classification), without pre-existing hepatopathy, HE beginning within \<26 weeks)
• or ACLF (≥ grade 1 from CANONIC criteria)
• with clinical HE (grade 1-4 of West-Haven classification) on the day of enrolment

You may not qualify if:

• age \< 18 years
• absence of HE
• LT without pre-existing HE
• patients who already undergone a LT
• other cause of neurological impairment
• Legally protected person

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Hepatic Encephalopathy; Liver Failure, Acute; Acute-On-Chronic Liver Failure

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Nicolas WEISS, MD, PhD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: March 16, 2023
• Study Start: September 1, 2023
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share