Anti HLA alloimmunization against the donor evaluated by the detection of anti-donor specific antibodies (DSA) is an underestimated factor in liver transplantation and may contribute to dysfunction and graft loss , especially among candidates for retransplantation, that have major immunization.

This study will analyzed immunization markers at the time of liver retransplantation and systematically in patients follow-up. This will allow to characterize the histological lesions due to humoral immunization, to establish further investigations and to adapt early immunosuppressive therapy.

Humoral rejection, related to immunization of the patient against the graft, is diagnosed by the presence of DSA. This serious complication, responsible for dysfunction and graft loss in kidney and heart transplant, is treated by strengthening the immunosuppressive treatment. Humoral rejection is poorly characterized in liver transplantation, but might explain the severe dysfunctions and misunderstood losses of liver transplant. In a preliminary study after liver transplantation, it was observed that the presence of DSAs was more common among patients with unexplained dysfunction (n = 22) compared to patients without dysfunction (n = 69) (95% versus 51%). After liver transplantation, 20% of patients are immunized, against 50% after retransplantation, and after retransplantation, approximately 40% of patients present with graft dysfunction within 2 years.

The role of humoral rejection in graft lesion and loss is unknown after liver transplantation because DSAs are not evaluated and histological lesions associated with DSAs are not analyzed. It is essential to characterize the humoral rejection in liver transplantation or after liver retransplantation (highly immunized population) and immunization markers that are responsible, for early management of this complication by an increased immunosuppressive therapy as it is done for kidney and heart transplantation. This could limit the progression to graft loss.

A specific anti HLA immunization against the donor (DSA - Donor Specific Antibodies) is an underestimated factor in liver transplantation and may contribute to dysfunction and loss of liver graft, especially among candidates for retransplantation, stronger immune.

This study will look for these markers of immunization at the time of liver retransplantation and systematically in patients follow-up. This will allow to characterize the histological lesions, to establish further investigations and to adapt early immunosuppressive therapy.

Methodology, experimental design: prospective, multicenter study. Results of anti HLA antibodies and DSA will not be given not to influence the teams on patient treatment.

Inclusion in the pre-retransplantation visit : obtaining of the informed consent, HLA and anti-HLA antibodies, HLA Typing.

Visit before-ReTH: HLA antibodies and DSA Visit 1 (day of transplant): Standard biology, HLA antibodies and DSA, Crossmatch, Histological analysis of liver de-transplantation locally and centralized.

Visits 2 and 3 (months 1 and 3 post retransplantation) : Standard biology, anti-HLA antibodies and DSA, liver Doppler Ultrasound (as usual the center).

Visits 4 and 5 (months 12 and 24 post retransplantation), and in case of unexplained hepatic dysfunction: Standard biology, HLA antibodies and DSA, liver Doppler-Ultrasound, Fibroscan and hepatic puncture biopsy : histological analysis on site and centralized.

Number of subjects required: 100 patients to be included (200 patients eligible to be selected in pre-transplant consultation for 100 patients retransplanted to include).

Total study duration: up to 6 years (3 years for inclusion and 3 years of follow-up - up to 1 year pre waiting Reth and 2 years post-transplant) Inclusion period: 2 years Duration of participation for a patient: up to 3 years (1 year maximum pre retransplantation waiting + 2 years after transplantation)

Number of participating centers: 11

Inclusion Criteria:

• Age ≥ 18 years with no upper age limit,
• Candidate for a liver retransplantation, whatever the indication, the period or the number of retransplantation
• Recipient of a social protection scheme or entitled
• Signature of informed consent

Exclusion Criteria:

• HIV positive patient,
• Multi-organ transplantation.