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Review
. 2025 Apr;45(4):e16142.
doi: 10.1111/liv.16142. Epub 2024 Nov 4.

New Scenarios in Liver Transplantation for Hepatocellular Carcinoma

Ezequiel Mauro  1   2 , Manuel Rodríguez-Perálvarez  2   3 , Antonio D'Alessio  4   5 , Gonzalo Crespo  2   6 , Federico Piñero  7 , Eleonora De Martin  8 , Jordi Colmenero  2   6 , David James Pinato  4   5 , Alejandro Forner  1   2
Affiliations
Review

New Scenarios in Liver Transplantation for Hepatocellular Carcinoma

Ezequiel Mauro et al. Liver Int. 2025 Apr.

Abstract

Background and aims: Despite liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC), particularly in patients with impaired liver function, the shortage of donors has forced the application of very restrictive criteria for selecting ideal candidates for whom LT can offer the best outcome. With the evolving LT landscape due to the advent of direct-acting antivirals (DAAs) and the steady increase in donors, major efforts have been made to expand the transplant eligibility criteria for HCC. In addition, the emergence of immune checkpoint inhibitors (ICIs) for the treatment of HCC, with demonstrated efficacy in earlier stages, has revolutionized the therapeutic approach for these patients, and their integration in the setting of LT is challenging. Management of immunological compromise from ICIs, including the wash-out period before LT and post-LT immunosuppression adjustments, is crucial to balance the risk of graft rejection against HCC recurrence. Additionally, the effects of increased immunosuppression on non-hepatic complications must be understood to prevent them from becoming obstacles to long-term OS.

Methods and results: In this review, we will evaluate the emerging evidence and its implications for the future of LT in HCC. Addressing these novel challenges and opportunities, while integrating the current clinical evidence with predictive algorithms, would ensure a fair balance between individual patient needs and the overall population benefit in the LT system.

Keywords: HCC; immunotherapy; liver transplant.

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Conflict of interest statement

  1. ‐

    E. Mauro: Received lecture fees from Roche and Sirtex, and travel funding from MSD.

  2. ‐

    M. Rodríguez‐Perálvarez: Received lecture fees from Astellas, Chiesi, and Advanz Pharma.

  3. ‐

    A. D'Alessio: Received educational support for congress attendance from Roche, and consultancy fees from Roche, Astrazeneca, and Chugai.

  4. ‐

    The authors declare no conflicts of interest.

  5. ‐

    F. Piñero: Received lecture fees, advisory board and grants from ROCHE, BAYER, LKM Knight, RAFFO and Astrazeneca.

  6. ‐

    E. De Martin: Received lecture and consultancy fees from IPSEN, GSK, Chiesi, Astellas

  7. ‐

    J. Colmenero: Received lecture fees and travel grants from Chiesi and Astellas.

  8. ‐

    D.J. Pinato: Received lecture fees from Astra Zeneca, Roche, EISAI, Boston Scientific, IPSEN and Bayer Healthcare, travel expenses from BMS, Roche, EISAI and Bayer Healthcare; consulting fees for Mina Therapeutics, iTeos, Avamune, EISAI, Roche, IPSEN, DaVolterra, Starpharma, Mursla and Astra Zeneca; received research funding (to institution) from MSD, GSK and BMS.

  9. ‐

    A. Forner: Received lecture fees from Gilead, Boston Scientific, Roche, and MSD, also consultancy fees from Bayer, AstraZeneca, Roche, SIRTEX, AB Exact Science and Guerbert.

Figures

FIGURE 1
FIGURE 1
Impact of donor availability on liver transplant system efficiency: Balancing waiting list mortality and 5‐year post‐transplant survival. LT, liver transplantation; OS, overall suvival; WL, waiting list.
FIGURE 2
FIGURE 2
A brief overview of liver transplant selection models for hepatocellular carcinoma. OS, overall survival; rHCC, recurrence rates after transplantation.
FIGURE 3
FIGURE 3
Main drivers of survival after liver transplantation. ESLD, end stage liver disease; HCC, hepatocellular carcinoma.
See this image and copyright information in PMC

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