Correlation Between Pre-transplant ICI Exposure and Post-transplant Graft Rejection

Study Overview
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Brief Summary
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Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC. The combination of the ICI and other treatment regimens (Anti-VEGF, locoregional therapies et al) produced superior results in patients with advanced-stage HCC compared to those treated with traditional therapeutic regimens. Liver transplantation (LT) offers excellent long-term outcomes for certain patients with HCC. However, the immune-stimulating property of ICIs may lead to rejection and even graft loss, damping their use in treating HCC before liver transplantation. Therefore, it is worthwhile to explore the relationship between exposure to ICIs before LT and the incidence of graft rejection and rejection-related death or graft loss after LT.

Detailed Description
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This will be a retrospective and observational study, which will analyze the correlation between the use of ICIs and incidences of graft rejection and rejection-related death or graft loss after LT in consecutive recipients with LT for HCC at the Organ Transplantation Center of Sun Yat-sen Memorial Hospital of Sun Yat-sen University. The primary aim of this study is to analyze the correlation between pretransplant exposure to ICIs and incidences of graft rejection and rejection-related death or graft loss within 1 year after liver transplantation. The secondary aim is to analyze the risk factors for graft rejection and to explore the correlation between ICI exposure and posttransplantation complication, such as incidences of early allograft dysfunction (EAD), bleeding, infection, biliary and vascular complications et al. The exploratory aim is to identify potential biomarkers in predicting graft rejection, such as subsets of lymphocytes and cytokines et al.

Official Title
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Correlation Between Exposure to Immune Checkpoint Inhibitors Before Liver Transplantation for Hepatocellular Carcinoma and Post-transplant Graft Rejection

Conditions
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Graft Rejection, Hepatocellular Carcinoma, Immunotherapy, Immune Checkpoint Inhibitor

Intervention / Treatment
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* Drug: Immune checkpoint inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Written informed consent must be obtained prior to any data collection. Patients must have pathologically or cytologically or by radiological criteria proven hepatocellular carcinoma based on the AASLD practice guidelines. All patients receiving liver transplantation for HCC. Exclusion Criteria Cholangiocellular carcinoma, combined hepatocellular and cholangiocarcinoma, and other rare types of liver cancer that are confirmed by histology/cytology. Patients with incomplete follow-up data

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ICI group<br>Recipients with exposure to immune checkpoint inhibitors before liver transplantation | Drug: Immune checkpoint inhibitor<br>* Immune checkpoint inhibitors work by blocking checkpoint proteins from binding with their partner proteins. This prevents the off signal from being sent, allowing the T cells to kill cancer cells.One such drug acts against a checkpoint protein called CTLA-4. Other immune checkpoint inhibitors act against a checkpoint protein called PD-1 or its partner protein PD-L1.<br>* Other names: Anti-PD-1; Anti-PD-L1; Anti-CTLA-4;|
| non-ICI group<br>Recipients without exposure to immune checkpoint inhibitors before liver transplantation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft rejection | In this study, rejection was be defined as the elevation of transaminase during the recovery of liver function after LT (transaminases should gradually return to normal levels) or suddenly abnormal elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2 times the upper limit that can be reversed by adjusting the immunosuppression regimen. Hepatic artery or portal vein thrombosis, drug toxicity or other factors should be excluded as the reason for liver function injury. Liver biopsies were not necessary for the diagnosis of rejection. The rejection activity index (RAI) was scored according to the Banff criteria to record the severity of acute rejection. An RAI score of 4-5 was defined as mild rejection, 6-7 was defined as moderate rejection, and 8-9 was defined as severe rejection. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft loss | Rejection related graft loss | 1 year | 
| Hospital death | rejection related death | 1 year | 
| Early allograft dysfunction (EAD) | EAD is defined by the presence of one or more of the following: total bilirubin ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST > 2,000 IU/L within the first 7 days | First 7 days after liver transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, liver transplantation, Immune checkpoint inhibitor, Graft rejection