Microbiota Study in Liver Transplanted Patients

NCT03507140 | Completed

• 1 other identifier: 38RC17.332
• Study Type: observational
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Many studies describe the relationship between microbiota alteration and the occurrence of metabolic, alcoholic or inflammatory liver diseases. Nevertheless, the modifications of microbiota during liver transplantation (LT) as well as its implication are poorly studied. Similarly, only the intestinal microbiota is studied in this context, and no data are available on the biliary microbiota, even if it is known that bile microbiota can interfere with hepatobiliary diseases. This study proposes a clinical and biological in-depth follow-up with multiple sampling of liver transplanted patients to study biliary and intestinal microbiota alterations along LT, as well as bile acids metabolism in corresponding fluids. Indeed, in recipient samples as saliva, blood, urine, and feces can be taken before LT, and surgeons can easily perform bile sampling during LT. In donors all samples can be taken during liver removal. This offers the opportunity to have a microbiotic landscape of individuals without liver disease (donor), and patients suffering from a chronic liver disease or a liver cancer before and after transplantation. Also, in Grenoble University hospital, in case of biliary anastomotic incongruence, a biliary stent is placed during LT in 60% of recipients. This stent is removed by endoscopic retrograde cholangiopancreatography (ERCP) within 6 months after LT, offering a second opportunity to obtain bile samples in transplanted patients, after the early post-LT period. Patients who do not require a biliary stent will also be included for the study of secondary objectives, as intestinal microbiota is very poorly characterized in liver transplanted patients too. A portion of the patients without biliary stent, may also develop an anastomotic biliary stricture requiring an ERCP. If this ERCP is realized within the follow-up period of the study, the patient will also be included in the primary objective of the study. These multiple and sequential samples will allow a complete analysis of microbiota changes in LT patients and aim to answer to 3 questions:

1. 1.What are the modifications of intestinal and biliary microbiomes during LT?
2. 2.What is the influence of bile acids' composition on intestinal and biliary microbiota?
3. 3.What are the relationships between microbiome alterations and the emergence of LT complications?

Conditions

Cirrhosis; Hepatocellular Carcinoma; Liver Transplant; Microbiota

Keywords

cirrhosis; hepatocellular carcinoma; Liver transplantation; Microbiota

Outcome Measures

Primary Outcomes (1)

• Comparison of the relative abundance of pathobionts and symbionts before and 6 months after liver transplantation, in the bile of recipients.

  Beneficial bacterias/pathobionts ratio before and 6 months after liver transplantation in the bile of recipients.

  During LT and 6 months after LT

Secondary Outcomes (11)

• Comparison of the relative abundance of pathobionts and beneficial bacteria at the time, and 6 months after liver transplantation, in the feces of recipients.

  Before LT (6 months maximum) and 6 months after LT

• Comparison of bile microbial diversity at the time, and 6 months after liver transplantation, in LT recipients.

  During LT and 6 months after LT

• Comparison of fecal microbial diversity before, and 6 months after liver transplantation, in LT recipients.

  Before LT (6 months maximum) and 6 months after LT

• Study the correlation between bile microbiota of donors and recipients after LT.

  During LT and 6 months after LT

• Study the correlation between fecal microbiota of donors and recipients after LT.

  Before LT (6 months maximum) and 6 months after LT

Interventions

Multiple sampling OTHER

Bile, saliva, feces, urine et blood samples before and after liver transplantation in recipients. Bile, saliva, feces, urine et blood samples during liver removal in donors.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients registered on the waiting list fo liver transplantation

You may qualify if:

• Recipients:
• Age ≥ 18 years old
• Absence of LT contraindications
• Patient undergoing liver transplantation
• Patient legally able to give written consent.
• Person affiliated to social security
• Donors:
• Cadaveric-donor liver transplantation

You may not qualify if:

• Living-related liver transplantation
• LT contraindications
• All subjects protected by articles L1121-5 and L1121-8 of French public health law (Subject under administrative or judicial control, person who are protected under the act, person hospitalized without their consent, prisoners and pregnant or breast-feeding women).

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

CHU de GRENOBLE ALPES

Grenoble, 38100, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Bile, blood, saliva, feces and urine in donor and recipients

MeSH Terms

Conditions

Fibrosis; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Gael ROTH, MD

  GRENOBLE ALPES UNIVERSITY HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 5, 2018
• First Posted: April 24, 2018
• Study Start: April 16, 2019
• Primary Completion: November 9, 2023
• Study Completion: March 27, 2024
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)