Evidence map›Paper›PMID 38996924›Full record

SynthesisJournal of hepatology2025

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

Mohammad Saeid Rezaee-Zavareh, Yee Hui Yeo, Tielong Wang, Zhiyong Guo, Parissa Tabrizian, Stephen C Ward, Fatma Barakat, Tarek I Hassanein, Shravan Dave, Veeral Ajmera and 35 more

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Journal of hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Guideline
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  3. Prognostic significance of systemic immune-inflammation index in hepatocellular carcinoma: a meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

45 authors.

Mohammad Saeid Rezaee-ZavarehMiddle East Liver Diseases Center, Tehran 1417935840, Iran.
Yee Hui YeoKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles 90048, CA, USA.
Tielong WangOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
Zhiyong GuoOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
Parissa TabrizianRecanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY, USA.
Stephen C WardDepartment of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Fatma BarakatSouthern California Liver Centers, 131 Orange Avenue, Suite 101, Coronado, CA, 92118, USA.
Tarek I HassaneinSouthern California Liver Centers, 131 Orange Avenue, Suite 101, Coronado, CA, 92118, USA.
Shravan DaveDivision of Gastroenterology & Hepatology, Department of Medicine, University of California, San Diego, La Jolla CA, USA.
Veeral AjmeraDivision of Gastroenterology & Hepatology, Department of Medicine, University of California, San Diego, La Jolla CA, USA.
Sherrie BhooriHPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Vincenzo MazzaferroHPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Department of Oncology, and Hemato-Oncology University of Milan, Milan, Italy.
David M H ChascsaDivision of Gastroenterology and Hepatology, Mayo Clinic Arizona, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA; Transplant Center, Mayo Clinic Arizona, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA.
Margaret C LiuDivision of Gastroenterology and Hepatology, Mayo Clinic Arizona, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA.
Elizabeth S AbyDivision of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN, USA.
John R LakeDivision of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN, USA.
Miguel SogbeLiver Unit and HPB Oncology Area, Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
Bruno SangroLiver Unit and HPB Oncology Area, Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
Maen AbdelrahimSection of GI Oncology, Department of Medical Oncology, Houston Methodist Neal Cancer Center, Houston, TX 77030, USA; Cockrell Center of Advanced Therapeutics Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Internal Medicine, Weill Cornell Medical College, New York, NY 10021, USA.
Abdullah EsmailSection of GI Oncology, Department of Medical Oncology, Houston Methodist Neal Cancer Center, Houston, TX 77030, USA; Cancer Clinical Trials, Houston Methodist Research Institute, Houston, TX 77030, USA.
Andreas SchmidererDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Yasmina ChouikCancer Research Center of Lyon (CRCL), INSERM U1052, Centre National de la Recherche Scientifique UMR5286, Lyon, France; Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
Mark RudolphDivision of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
Davendra SohalDivision of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
Heloise GiudicelliAP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France.
Manon AllaireAP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France; INSERM UMR 1138, Centre de recherche des Cordeliers, 75006 Paris, France.
Mehmet AkceDivision of Hematology and Oncology, Department of Medicine, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA.
Jessica GuadagnoDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Clara Y TowDivision of Hepatology, Montefiore Medical Center, Bronx, New York; Albert Einstein College of Medicine, Bronx, NY, USA.
Hatef MassoumiDivision of Hepatology, Northwell 261 East 78th Street, Floor 4, New York, NY 10075, USA.
Paolo De SimoneHepatobiliary Surgery and liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, Pisa, 56124, Italy.
Elise KangDepartment of Pediatrics, Division of Pediatric Hematology/Oncology/SCT, Columbia University Irving Medical Center, New York, New York, USA.
Robyn D GartrellDepartment of Pediatrics, Division of Pediatric Hematology/Oncology/SCT, Columbia University Irving Medical Center, New York, New York, USA; Department of Oncology, Division of Pediatric Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Mercedes MartinezDepartment of Pediatrics. Vagelos College of Physician and Surgeons. Columbia University, USA.
Ricardo Paz-FumagalliMayo Clinic Florida, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.
Beau B ToskichDivision of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
Nguyen H TranDepartment of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Gabriela Azevedo SolinoEscola Superior de Ciências da Santa Casa de Misericórdia de Vitória - Department of Internal Medicine - Vitória/ES - Brazil.
Dra Mariana Poltronieri PachecoEscola Superior de Ciências da Santa Casa de Misericórdia de Vitória - Department of Gastroenterology and Hepatology - Vitória/ES - Brazil.
Richard S KalmanDivision of Hepatology, Department of Medicine, Einstein Healthcare Network, Philadelphia, Pennsylvania, USA.
Vatche G AgopianThe Dumont-University of California, Los Angeles, Transplant Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Neil MehtaDivision of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, USA.
Neehar D ParikhDivision of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
Amit G SingalDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Ju Dong YangKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles 90048, CA, USA; Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles 90048, CA, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles 90048, CA, USA. Electronic address: judong.yang@cshs.org.

Funding

Working to Eliminate Care Disparities in Liver Cancer in Southeast Asian Americans: Transportation and Other Social Determinants of Health.K23MD017217 · NIMHD · MAYO CLINIC ROCHESTER · PI Nguyen H Tran · 2022 to 2026
$818k
Novel circulating biomarker digital scores for assessing treatment response in liver cancerK08CA259534 · NCI · CEDARS-SINAI MEDICAL CENTER · PI YANG, JU DONG · 2022 to 2024
$807k
NCI NIH HHS K08 CA259534NIMHD NIH HHS K23 MD017217
6 · The paper itself

Abstract

BACKGROUND &

aimsTreatment 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.

methodsIn 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.

resultsAmong 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).

conclusionPatients 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.

Indexed as

Carcinoma, HepatocellularGraft RejectionImmune Checkpoint InhibitorsLiver NeoplasmsLiver TransplantationFemaleHumansMaleMiddle AgedNeoplasm Recurrence, LocalRisk FactorsTreatment OutcomeImmune Checkpoint InhibitorsGraft RejectionHepatocellular CarcinomaImmune Checkpoint InhibitorsLiver NeoplasmsLiver TransplantationRecurrence

Identifiers

PMID38996924
PMCPMC11655254

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.