Graft RejectionNCT05913583
Correlation Between Pre-transplant ICI Exposure and Post-transplant Graft Rejection
An observational study of Graft Rejection and Hepatocellular Carcinoma, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Graft Rejection, Hepatocellular Carcinoma, Immunotherapy
- What is being tested?
- Immune checkpoint inhibitor
- How many people
- 160 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2023to 1 Sep 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: A retrospective cohort study will be performed on consecutive HCC patients who underwent LT for HCC. The pretransplant parameters, such as AFP, tumor status, BMI, and etiology et al, as well as posttransplant parameters, such as graft rejection, EAD, hospital death et al, will be analyzed.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Organ Transplantation Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University,
Guangzhou, Guangdong, 376032
Li PANG, PhD, 13622860325, leepang@connect.hku.hk
Chao LIU, PhD
About this study
Official title: Correlation Between Exposure to Immune Checkpoint Inhibitors Before Liver Transplantation for Hepatocellular Carcinoma and Post-transplant Graft Rejection
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.
Read the detailed description
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.
- Being tested
- Immune checkpoint inhibitor
- Keywords
- hepatocellular carcinoma, liver transplantation, Immune checkpoint inhibitor, Graft rejection
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immune checkpoint inhibitorDrug
Also called Anti-PD-1; Anti-PD-L1; Anti-CTLA-4
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.
| Study group | Role | What they receive |
|---|---|---|
| ICI group | Recipients with exposure to immune checkpoint inhibitors before liver transplantation Receives: Drug: Immune checkpoint inhibitor | |
| non-ICI group | Recipients without exposure to immune checkpoint inhibitors before liver transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (3)
Graft loss
Rejection related graft loss
Measured: 1 year
Hospital death
rejection related death
Measured: 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
Measured: First 7 days after liver transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2023
- Study start1 Apr 2023
- Primary completion1 Aug 2023 (estimated)
- Study completion1 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Graft RejectionStudies of the same condition, open and under way.
- More trials run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chao Liu, PhD, Principal investigator, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05913583
- Sponsor's protocol ID
- SYSKY-2023-224-01
- Status last verified
- Apr 2023
- First submitted
- 24 May 2023
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schwacha-Eipper B, Minciuna I, Banz V, Dufour JF. Immunotherapy as a Downstaging Therapy for Liver Transplantation. Hepatology. 2020 Oct;72(4):1488-1490. doi: 10.1002/hep.31234. No abstract available.
PubMed 32171041Tran NH, Munoz S, Thompson S, Hallemeier CL, Bruix J. Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti-VEGF/TKI and immunotherapy. Hepatology. 2022 Oct;76(4):1203-1218. doi: 10.1002/hep.32613. Epub 2022 Jul 30.
PubMed 35765265Katariya NN, Lizaola-Mayo BC, Chascsa DM, Giorgakis E, Aqel BA, Moss AA, Uson Junior PLS, Borad MJ, Mathur AK. Immune Checkpoint Inhibitors as Therapy to Down-Stage Hepatocellular Carcinoma Prior to Liver Transplantation. Cancers (Basel). 2022 Apr 19;14(9):2056. doi: 10.3390/cancers14092056.
PubMed 35565184Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, Pikarsky E, Zhu AX, Finn RS. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022 Mar;19(3):151-172. doi: 10.1038/s41571-021-00573-2. Epub 2021 Nov 11.
PubMed 34764464Pang L, Xu L, Chen Z, Liu Y, Ding T, Ye Y, Lu X, Gu G, Lin H, Wu W, Man K, Liu C. Short-term prognosis of recipients with pretransplant exposure to immune checkpoint inhibitors after liver transplantation for hepatocellular carcinoma: A retrospective cohort study. Liver Res. 2025 Mar 8;9(3):221-230. doi: 10.1016/j.livres.2025.03.001. eCollection 2025 Sep.
PubMed 41112510
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation Between Exposure to Immune Checkpoint Inhibitors Before Liver Transplantation for Hepatocellular Carcinoma and Post-transplant Graft Rejection
- ClinicalTrials.gov ID
- NCT05913583
- Acronym / sponsor ID
- SYSKY-2023-224-01
- Keywords
- hepatocellular carcinoma, liver transplantation, Immune checkpoint inhibitor, Graft rejection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 1 Apr 2023 (actual)
- Primary completion
- 1 Aug 2023 (estimated)
- Study completion
- 1 Sep 2023 (estimated)
- First posted
- 22 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ICI group | – | Drug: Immune checkpoint inhibitorRecipients with exposure to immune checkpoint inhibitors before liver transplantation |
| non-ICI group | – | –Recipients without exposure to immune checkpoint inhibitors before liver transplantation |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A retrospective cohort study will be performed on consecutive HCC patients who underwent LT for HCC. The pretransplant parameters, such as AFP, tumor status, BMI, and etiology et al, as well as posttransplant parameters, such as graft rejection, EAD, hospital death et al, will be analyzed.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immune checkpoint inhibitorAlso: Anti-PD-1; Anti-PD-L1; Anti-CTLA-4Immune 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. | Drug | ICI group |
Primary outcome
Graft rejection
Time frame: 1 year
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.
3 secondary outcomes
Graft loss
Time frame: 1 year
Hospital death
Time frame: 1 year
Early allograft dysfunction (EAD)
Time frame: First 7 days after liver transplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Background: PubMed 32171041Schwacha-Eipper B, Minciuna I, Banz V, Dufour JF. Immunotherapy as a Downstaging Therapy for Liver Transplantation. Hepatology. 2020 Oct;72(4):1488-1490. doi: 10.1002/hep.31234. No abstract available.
- Background: PubMed 35765265Tran NH, Munoz S, Thompson S, Hallemeier CL, Bruix J. Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti-VEGF/TKI and immunotherapy. Hepatology. 2022 Oct;76(4):1203-1218. doi: 10.1002/hep.32613. Epub 2022 Jul 30.
- Background: PubMed 35565184Katariya NN, Lizaola-Mayo BC, Chascsa DM, Giorgakis E, Aqel BA, Moss AA, Uson Junior PLS, Borad MJ, Mathur AK. Immune Checkpoint Inhibitors as Therapy to Down-Stage Hepatocellular Carcinoma Prior to Liver Transplantation. Cancers (Basel). 2022 Apr 19;14(9):2056. doi: 10.3390/cancers14092056.
- Background: PubMed 34764464Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, Pikarsky E, Zhu AX, Finn RS. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022 Mar;19(3):151-172. doi: 10.1038/s41571-021-00573-2. Epub 2021 Nov 11.
- Derived from this study: PubMed 41112510Pang L, Xu L, Chen Z, Liu Y, Ding T, Ye Y, Lu X, Gu G, Lin H, Wu W, Man K, Liu C. Short-term prognosis of recipients with pretransplant exposure to immune checkpoint inhibitors after liver transplantation for hepatocellular carcinoma: A retrospective cohort study. Liver Res. 2025 Mar 8;9(3):221-230. doi: 10.1016/j.livres.2025.03.001. eCollection 2025 Sep.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chao Liu, PhD principal investigator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Graft Rejection and Hepatocellular Carcinoma, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Li PANG, PhD (+86 13622860325, pangli5@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Graft rejection (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05913583, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.