Study of Covalently Closed Circular DNA (cccDNA) in Liver Transplant Patients With B Virus Markers

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to validate in the context of liver transplantation, the interest of the cccDNA assay technique developed by the team of Professor Zoulim (INSERM U1052) on liver biopsy and correlate this assay cccDNA in hepatitis B virus (HBV) viral load and serum liver through several groups of patients at transplantation (on graft and native liver explant) and after transplantation.

Official Title
-----------------
Study of cccDNA in Liver Transplant Patients With B Virus Markers

Conditions
-----------------
Liver Transplantation

Intervention / Treatment
-----------------
* Biological: cccDNA assay on liver biopsy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient registered on the national Organ Transplant Waiting List for liver transplantation Indication of transplantation : Alcoholic related disease without serum anti-hepatitis B core antibody (HBc) (less than 4 weeks) OR - HCV related disease without serum anti-HBc antibody (less than 4 weeks) OR - Patients who sign consent for liver transplantation from hepatitis B core antibody positive donors OR - HBV related disease with positive serum HBs antigen (with or without HBV replication measured by polymerase chain reaction (PCR) within 6 months prior transplantation) Signed consent form Patient with a social cover Patient not covered by any measure of legal protection Exclusion Criteria: Co-infection with HIV, hepatitis delta virus (HDV), HBV (for control arm), HCV (for Test arm) - Positive serology within the4 weeks before inclusion Patient covered by any measure of legal protection informed consent not signed

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with alcoholic or hepatitis C virus related disease<br>cccDNA assay on liver biopsy in patients with liver transplantation for alcoholic disease or hepatitis C virus (HCV) related disease, without contact with HBV | Biological: cccDNA assay on liver biopsy<br>* cccDNA assay will be performed on liver biopsies at different times : During transplantation : Liver biopsy of explant and graft and virological biology Between M1 to M3 after transplantation : Liver biopsy between 1 to 3 months after transplantation M12 : Liver biopsy 12 months after transplantation<br>|
| Hepatitis B core antibody positive donors<br>cccDNA assay on liver biopsy in patients who receive liver from hepatitis B core antibody positive donors | Biological: cccDNA assay on liver biopsy<br>* cccDNA assay will be performed on liver biopsies at different times : During transplantation : Liver biopsy of explant and graft and virological biology Between M1 to M3 after transplantation : Liver biopsy between 1 to 3 months after transplantation M12 : Liver biopsy 12 months after transplantation<br>|
| HBV patients<br>cccDNA assay on liver biopsy in patient with liver transplantation for chronic hepatitis B, with or without HBV replication | Biological: cccDNA assay on liver biopsy<br>* cccDNA assay will be performed on liver biopsies at different times : During transplantation : Liver biopsy of explant and graft and virological biology Between M1 to M3 after transplantation : Liver biopsy between 1 to 3 months after transplantation M12 : Liver biopsy 12 months after transplantation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cccDNA rate on native explant and liver transplant during transplantation and on liver biopsy | cccDNA rate will be assessed on native explant and liver transplant during transplantation and on liver biopsy (between M1 to M3 and 12 months (M12) after transplantation) to study the colonization of new hepatocytes by HBV | 1 year after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between cccDNA rate and serologic status | Correlation of cccDNA rate with serologic and virologic status (AgHBe, HBV DNA, ...) at the moment of the transplantation and during post-transplantation period and HBV recurrence | 1 year after transplantation | 
| Correlation between cccDNA rate and virologic status | Correlation of cccDNA assay with serologic and virologic status (AgHBe, HBV DNA, ...) will be assessed at the moment of the transplantation and during post-transplantation period and HBV recurrence | 1 year after transplantation | 
| Correlation between cccDNA rate and patient's treatment | Correlation of cccDNA rate with patients' treatments will be assessed at the moment of the transplantation and during post-transplantation period and HBV recurrence | 1 year after transplantation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Liver transplantation, HBV, cccDNA