Immunization Anti HLA in the Liver Transplant Recipients (DSATH)
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Risk of graft failure at 24 months (Odds Ratio) depending on the presence of DSA at retransplantation.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •HIV positive patient,
- •Multi-organ transplantation.
研究组 & 干预措施
Liver retransplantation
- Donor specific antibodies :Additional samples for Donor specific at each visit
- Serum bank : Additional samples for serum bank at each visit if possible
- DNA banq : Additional sample for DNA banq at inclusion visit if possible
- Liver biopsy :Liver biopsy at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
- Liver ultrasounds and Fibroscan : Liver ultrasounds and Fibroscan at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
干预措施: Donor specific antibodies (Biological)
Liver retransplantation
- Donor specific antibodies :Additional samples for Donor specific at each visit
- Serum bank : Additional samples for serum bank at each visit if possible
- DNA banq : Additional sample for DNA banq at inclusion visit if possible
- Liver biopsy :Liver biopsy at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
- Liver ultrasounds and Fibroscan : Liver ultrasounds and Fibroscan at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
干预措施: Serum bank (Biological)
Liver retransplantation
- Donor specific antibodies :Additional samples for Donor specific at each visit
- Serum bank : Additional samples for serum bank at each visit if possible
- DNA banq : Additional sample for DNA banq at inclusion visit if possible
- Liver biopsy :Liver biopsy at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
- Liver ultrasounds and Fibroscan : Liver ultrasounds and Fibroscan at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
干预措施: DNA bank (Biological)
Liver retransplantation
- Donor specific antibodies :Additional samples for Donor specific at each visit
- Serum bank : Additional samples for serum bank at each visit if possible
- DNA banq : Additional sample for DNA banq at inclusion visit if possible
- Liver biopsy :Liver biopsy at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
- Liver ultrasounds and Fibroscan : Liver ultrasounds and Fibroscan at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
干预措施: Liver biopsy (Procedure)
Liver retransplantation
- Donor specific antibodies :Additional samples for Donor specific at each visit
- Serum bank : Additional samples for serum bank at each visit if possible
- DNA banq : Additional sample for DNA banq at inclusion visit if possible
- Liver biopsy :Liver biopsy at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
- Liver ultrasounds and Fibroscan : Liver ultrasounds and Fibroscan at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
干预措施: Liver ultrasounds and Fibroscan (Procedure)
结局指标
主要结局
Risk of graft failure at 24 months (Odds Ratio) depending on the presence of DSA at retransplantation.
时间窗: 24 months after retransplantation
The graft failure is defined by abnormal hepatic tests (AST, ALT, GGT, PAL, total and conjugated bilirubin, PT, INR), and/or abnormal hepatic histology , and/or abnormal hepatic imagery.
次要结局
- Evaluate the association between the presence of DSA and fibrosis Fibroscan measured at 12 and 24 months. (Student t-test or non parametric test).(12 and 24 months after retransplantation)
- Evaluate the association between the presence of the DSA at retransplantation and histological abnormalities of the explant and graft. ( Pearson's chi-square test or Fischer exact test).(retransplantation, 12 and 24 months after retransplantation)
- Evaluate the association between the presence of the DSA at before retransplantation and biological abnormalities graft from the previous donor(9 months, 6 months, 3 months Before transplantation)
- Evaluate the association between the presence of the DSA at retransplantation and biological abnormalities graft at 1, 3, 12 and 24 months.( Pearson's chi-square test or Fischer exact test).(1, 3, 12 and 24 months after retransplantation)
- Evaluate the association between the number of acute rejection episodes and the presence of the DSA at retransplantation and their evolution (especially of recurrence).(Pearson's chi-square test or Fischer exact test).(24 months after retransplantation)