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Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

作者信息

Rezaee-Zavareh Mohammad Saeid, Yeo Yee Hui, Wang Tielong, Guo Zhiyong, Tabrizian Parissa, Ward Stephen C, Barakat Fatma, Hassanein Tarek I, Dave Shravan, Ajmera Veeral, Bhoori Sherrie, Mazzaferro Vincenzo, Chascsa David M H, Liu Margaret C, Aby Elizabeth S, Lake John R, Sogbe Miguel, Sangro Bruno, Abdelrahim Maen, Esmail Abdullah, Schmiderer Andreas, Chouik Yasmina, Rudolph Mark, Sohal Davendra, Giudicelli Heloise, Allaire Manon, Akce Mehmet, Guadagno Jessica, Tow Clara Y, Massoumi Hatef, De Simone Paolo, Kang Elise, Gartrell Robyn D, Martinez Mercedes, Paz-Fumagalli Ricardo, Toskich Beau B, Tran Nguyen H, Solino Gabriela Azevedo, Poltronieri Pacheco Dra Mariana, Kalman Richard S, Agopian Vatche G, Mehta Neil, Parikh Neehar D, Singal Amit G, Yang Ju Dong

机构信息

Middle East Liver Diseases Center, Tehran 1417935840, Iran.

Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles 90048, CA, USA.

出版信息

J Hepatol. 2025 Jan;82(1):107-119. doi: 10.1016/j.jhep.2024.06.042. Epub 2024 Jul 10.


DOI:10.1016/j.jhep.2024.06.042
PMID:38996924
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11655254/
Abstract

BACKGROUND & AIMS: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (IQR) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years 0.72, 95% CI 0.53-0.99, p = 0.044) and ICI washout time (aHR per 1 week 0.92, 95% CI 0.86-0.99, p = 0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p = 0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8] vs. 8.0 [9.0]; p = 0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p = 0.032). CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitor use prior to liver transplantation suggest acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without immune checkpoint inhibitor exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies.

摘要

相似文献

[1]
Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

J Hepatol. 2025-1

[2]
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J Hepatol. 2025-3

[3]
Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation.

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[4]
Risk of transplant rejection associated with ICIs prior to liver transplantation in HCC: A multicenter retrospective study.

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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Immune checkpoint inhibitors use in liver transplantation for hepatocellular carcinoma: a global cohort study.

BMC Med. 2025-9-2

[2]
Current knowledge about immunotherapy response after liver transplantation of patients with liver cancer.

J Liver Transpl. 2025-8

[3]
Management of hepatocellular carcinoma prior to liver transplantation: latest developments.

Hepat Oncol. 2025-12

[4]
Prognostic significance of systemic immune-inflammation index in hepatocellular carcinoma: a meta-analysis.

Clin Transl Oncol. 2025-8-19

[5]
Review Article: Liver Transplantation for Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors.

Aliment Pharmacol Ther. 2025-9

[6]
Neoadjuvant immunotherapy for resectable primary liver cancer (Review).

Oncol Lett. 2025-7-23

[7]
Managing hepatocellular carcinoma recurrence after liver transplantation: emerging role of immune checkpoint inhibitors.

Discov Oncol. 2025-7-28

[8]
Emerging Trends in Neoadjuvant Immunotherapy for Hepatocellular Carcinoma: A Focus on Liver Transplant Candidates.

Cancer Rep (Hoboken). 2025-7

[9]
Liver Transplantation for Colorectal Metastases: Impact of a Standardised Protocol for Patient Selection on Transplant Outcomes.

Cancers (Basel). 2025-6-19

[10]
The Concept of "Converse Therapeutic Hierarchy" for Patients with Hepatocellular Carcinoma.

Liver Cancer. 2025-5-10

本文引用的文献

[1]
Downstaging Hepatocellular Carcinoma with Checkpoint Inhibitor Therapy Improves Access to Curative Liver Transplant.

J Gastrointest Cancer. 2024-6

[2]
Immunotherapy before liver transplant in unresectable hepatocellular carcinoma: a case report.

J Gastrointest Oncol. 2023-12-31

[3]
Successful liver transplantation with ctDNA clearance after PD‑1 inhibitor plus FOLFOX‑HAIC treatment in HCC: A case report.

Oncol Lett. 2023-12-12

[4]
Abscopal downstaging of intermediate stage hepatocellular via combination cryoablation and immunotherapy with complete pathologic response.

Radiol Case Rep. 2023-12-16

[5]
Immunotherapy for transplantation of hepatocellular carcinoma: the next frontier in adjunctive therapy.

Curr Opin Organ Transplant. 2024-4-1

[6]
Advances and considerations in the use of immunotherapies for primary hepato-biliary malignancies.

Surg Oncol. 2024-2

[7]
Immunosuppression for older liver transplant recipients.

Transplant Rev (Orlando). 2024-1

[8]
Liver Transplantation.

N Engl J Med. 2023-11-16

[9]
Hepatocellular Carcinoma: The Role of Immunotherapy and Transplantation in the Era of Transplant Oncology.

Cancers (Basel). 2023-10-24

[10]
Immunotherapy and Liver Transplantation: The Future or the Failure?

Surg Clin North Am. 2024-2

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