NCT05913583

Brief 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. 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
160

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Apr 2023

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2023

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

May 24, 2023

Completed
29 days until next milestone

First Posted

Study publicly available on registry

June 22, 2023

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2023

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2023

Completed
Last Updated

June 22, 2023

Status Verified

April 1, 2023

Enrollment Period

4 months

First QC Date

May 24, 2023

Last Update Submit

June 21, 2023

Conditions

Graft RejectionHepatocellular CarcinomaImmunotherapyImmune Checkpoint Inhibitor

Keywords

hepatocellular carcinomaliver transplantationImmune checkpoint inhibitorGraft rejection

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Graft loss

    1 year

  • Hospital death

    1 year

  • Early allograft dysfunction (EAD)

    First 7 days after liver transplantation

Other Outcomes (2)

  • CD4 to CD8 T cell ratio

    1 year

  • pDC to mDC ratio

    1 year

Study Arms (2)

ICI group

Recipients with exposure to immune checkpoint inhibitors before liver transplantation

Drug: Immune checkpoint inhibitor

non-ICI group

Recipients without exposure to immune checkpoint inhibitors before liver transplantation

Interventions

Immune checkpoint inhibitorDRUG

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.

Also known as: Anti-PD-1; Anti-PD-L1; Anti-CTLA-4
ICI group

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
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.

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Organ Transplantation Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University,

Guangzhou, Guangdong, 376032, China

RECRUITING

Related Publications (5)

  • 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.

    PMID: 32171041BACKGROUND

  • Tran 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.

    PMID: 35765265BACKGROUND

  • Katariya 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.

    PMID: 35565184BACKGROUND

  • Llovet 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.

    PMID: 34764464BACKGROUND

  • Pang 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.

    PMID: 41112510DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesAntineoplastic Agents, ImmunologicalAntineoplastic AgentsTherapeutic Uses

Study Officials

  • Chao Liu, PhD

    Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Li PANG, PhD

CONTACT

+86 13622860325pangli5@mail.sysu.edu.cn

Leibo XU, PhD

CONTACT

+86-18819182396xuleibo3@mail.sysu.edu.cn

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
RETROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 24, 2023

First Posted

June 22, 2023

Study Start

April 1, 2023

Primary Completion

August 1, 2023

Study Completion

September 1, 2023

Last Updated

June 22, 2023

Record last verified: 2023-04

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)