ADDICTOlogical Intervention in LIVEr Transplantation Recipients
NCT Number: NCT06472973
Acronym: AddictoLIVE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Alcohol Associated Liver Disease|Liver Transplantation
Interventions: OTHER: Post-transplant addiction intervention
Sponsor: University Hospital, Montpellier
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 720
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-09
Completion Date: 2028-09
Locations: Besançon University Hospital, Besançon, France|Bordeaux University Hospital, Bordeaux, France|Clermont Ferrand University Hospital, Clermont-Ferrand, France|Grenoble University Hospital, Grenoble, France|Lille University Hospital, Lille, France|Lyon University Hospital, Lyon, France|Marseille University Hospital, Marseille, France|Montpellier University Hospital, Montpellier, 34000, France|Nice University Hospital, Nice, France|APHP Mondor, Paris, France|APHP Paul Brousse, Paris, France|APHP Salpetrière, Paris, France|Rennes University Hospital, Rennes, France|Strasbourg University Hospital, Strasbourg, France|Toulouse University Hospital, Toulouse, France|Tours University Hospital, Tours, France

Summary:
Transplantation for end-stage-liver disease (ESLD) in the context of Alcohol-Associated Liver Disease (AALD) has been increasing and represents the main indication for Liver Transplantation (LT) in the world. Alcohol Use Disorder (AUD) is considered a brain chronic disease and requires a transdisciplinary approach that includes medical treatment and behavioral interventions.

In the context of LT, alcohol relapse occurs in 26 % up to 50% of LT recipients. Among Liver transplant recipients for AALD, severe alcoholic relapse (defined as more than 3 alcoholic drinks per day for women and 4/day for men) after LT leads to impaired longterm survival due to recurrent alcoholic cirrhosis (RAC), cardiovascular events and de novo cancer.

Several strategies have been developed to prevent alcohol relapse. After LT, integrating an addiction team into the LT program has been advocated by the latest guidelines in Europe and the United States, in order to bring the management of alcohol-use disorder (AUD) in transplantation units, through the association of psychosocial and pharmacological interventions previously reported in AALD. However, those guidelines were based on descriptive studies, and the effect of this management needs to be confirmed through a randomized, controlled, multicenter study, involving centers that still do not include an addiction team in their LT programs.

This study will therefore assess prospectively and comparatively the impact of an addiction intervention after LT on return to alcohol use rates. We hypothesize that standardized targeted addiction monitoring of Liver Transplant recipients decreases the rates of alcohol relapse two years post-liver transplantation.

Primary Outcome Measures: Time to return to alcohol use, Time to return to alcohol use is defined by the time between discharge from Liver Transplantation (LT) hospitalization and alcohol relapse,it includes either:

* Severe relapse: alcohol intake of at least 4 units per day for men and 3 per day for women for at least 100 days;
* Regular relapse: no more than 21 units a week for men, 14 units a week for women, at least 10 times a month; Alcohol consumption will be collected using the alcohol timeline follow back (TLFB), the assessor will be blinded to the participant's arm allocation.

TLFB is a calandar used to asses the participant's alcohol intake, it evaluates their daily drinking and provides a report of their drinking pattern over a given time period.

The first TLFB assessment will be carried out one month after discharge from LT hospitalization, then every 2 months up to 2 years after discharge from LT hospitalization., During 2 years after discharge from Liver transplantation hospitalization
Secondary Outcome Measures: Return to alcohol use of the slip type, Alcohol use will be measured using the TLFB,the assessor will be blinded to the participant's arm allocation.

Slip type is defined by a unique excessive alcohol consumption (more than 4 alcohol drinks on a single occasion).

The first TLFB assessment will be carried out one month after discharge from LT hospitalization, then every 2 months up to 2 years after discharge from LT hospitalization., During 2 years after discharge from Liver transplantation hospitalization|Tobacco use, Tobacco use will be measured by relative reduction in the number of cigarettes smoked per day compared with baseline, and by smoking abstinence at 24 months after discharge from LT hospitalization, for at least one month. Tobacco use will be self reported by the participant during interviews with an assessor who is blinded to their arm allocation.

Tobacco use assessment will be carried out one month after discharge from LT hospitalization, then every 2 months up to 2 years after discharge from LT hospitalization., During 2 years after discharge from Liver transplantation hospitalization|Other psychoactive substances use, Psychoactive substances use (opiates, abuse drugs, psychostimulants or psychedelics ) will be self reported by the participant during interviews with an assessor who is blinded to their arm allocation.

Psychoactive substances use assessment will be carried out one month after discharge from LT hospitalization, then every 2 months up to 2 years after discharge from LT hospitalization., During 2 years after discharge from Liver transplantation hospitalization|Addiction therapies, Addiction therapies (behavioral, motivational therapy and medication) implemented in the intervention arm will be described., During 2 years after discharge from Liver transplantation hospitalization|Major significant clinical events, Major significant clinical events includes death, cardiovascular events (myocardial infarction, pulmonary embolism, stroke), De Novo cancer and graft rejection.

The occurrence of major significant clinical events will be collected during the participation period, time-to-event is defined as the time from LT until event or loss to follow-up or end of the study or death., During 2 years after discharge from Liver transplantation hospitalization|Biochemical liver tests, Biochemical liver tests ( Alanine transaminase ALT, Aspartate transaminase AST, gamma-glutamyl transferase GGT, alkaline phosphatase and bilirubin) evolution will be assessed.

Biochemical liver tests will be measured as X upper limit normal ULN, 3 months after discharge from LT hospitalization, then every 2 months up to 2 years after discharge from LT hospitalization., During 2 years after discharge from Liver transplantation hospitalization|Alcohol consumption biomarker ethanol/Peth), Alcohol use biomarker (Phosphatidylethanol/Peth) kinetics, tested 3 times a year, will be compared to self-reported alcohol consumption.

Blood phosphatidylethanol concentration is determined by liquid chromatography coupled to a tandem mass spectrometer., At 1 month, 11 or 13 months and at 24 months after discharge from Liver transplantation hospitalization|Liver fibrosis, Liver fibrosis will be assessed using liver stiffness measurement by pulse elastometry (Fibroscan) and expressed in kilopascal (kPa)., 2 years after discharge from Liver transplantation hospitalization|Evolution of cognitive disorders, Cognitive disorders will be measured using the Montreal Cognitive Assessment (MoCA) test which is a screening tool used to determine if there is any impairment in the participant's cognitive function, including their ability to understand, reason, and remember.

The MoCA score ranges from 0 to 30:

* 27-30: is considered normal
* 18-26: indicates the presence of mild cognitive impairment
* 10-17: indicates the presence of moderate cognitive impairment
* \< 10: indicates the presence of severe cognitive impairment

MoCA test will be carried out at inclusion, 3 months after discharge from LT hospitalization then every 2 months up to 2 years after discharge from LT hospitalization., During 2 years after discharge from Liver transplantation hospitalization|Mortality and alcohol-associated mortality rate, The occurrence of death (overall mortality and alcohol-associated mortality) will be collected during the participation period.

Time-to-death is defined as the time from LT until death., During 2 years after discharge from Liver transplantation hospitalization