Publicaciones científicas

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

10-jul-2024 | Revista: Journal of Hepatology

Mohammad Saeid Rezaee-Zavareh  1 , Yee Hui Yeo  2 , Tielong Wang  3 , Zhiyong Guo  3 , Parissa Tabrizian  4 , Stephen C Ward  5 , Fatma Barakat  6 , Tarek I Hassanein  6 , Dave Shravan  7 , Ajmera Veeral  7 , Sherrie Bhoori  8 , Vincenzo Mazzaferro  9 , David M H Chascsa  10 , Margaret C Liu  11 , Elizabeth S Aby  12 , John R Lake  12 , Miguel Sogbe  13 , Bruno Sangro  13 , Maen Abdelrahim  14 , Abdullah Esmail  15 , Andreas Schmiderer  16 , Yasmina Chouik  17 , Mark Rudolph  18 , Davendra Sohal  18 , Heloise Giudicelli  19 , Manon Allaire  20 , Mehmet Akce  21 , Jessica Guadagno  22 , Clara Y Tow  23 , Hatef Massoumi  24 , Paolo De Simone  25 , Elise Kang  26 , Robyn D Gartrell  27 , Mercedes Martinez  28 , Ricardo Paz-Fumagalli  29 , Beau B Toskich  30 , Nguyen H Tran  31 , Gabriela Azevedo Solino  32 , Dra Mariana Poltronieri Pacheco  33 , Richard S Kalman  34 , Vatche G Agopian  35 , Neil Mehta  36 , Neehar D Parikh  37 , Amit G Singal  38 , Ju Dong Yang  39


Background and aim: 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.

Materials and 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 (interquartile range [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% confidence interval [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 inhibitors use prior to liver transplantation suggests 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 ICI 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. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.

CITA DEL ARTÍCULO  J Hepatol. 2024 Jul 10:S0168-8278(24)02354-7. doi: 10.1016/j.jhep.2024.06.042

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