JHEP Reports (Oct 2021)

International study on the outcome of locoregional therapy for liver transplant in hepatocellular carcinoma beyond Milan criteria

  • Helena Degroote,
  • Federico Piñero,
  • Charlotte Costentin,
  • Andrea Notarpaolo,
  • Ilka F. Boin,
  • Karim Boudjema,
  • Cinzia Baccaro,
  • Aline Lopes Chagas,
  • Philippe Bachellier,
  • Giuseppe Maria Ettorre,
  • Jaime Poniachik,
  • Fabrice Muscari,
  • Fabrio Di Benedetto,
  • Sergio Hoyos Duque,
  • Ephrem Salame,
  • Umberto Cillo,
  • Adrián Gadano,
  • Claire Vanlemmens,
  • Stefano Fagiuoli,
  • Fernando Rubinstein,
  • Patrizia Burra,
  • Daniel Cherqui,
  • Marcelo Silva,
  • Hans Van Vlierberghe,
  • Christophe Duvoux,
  • Karim Boudjema,
  • Philippe Bachellier,
  • Filomena Conti,
  • Olivier Scatton,
  • Fabrice Muscari,
  • Ephrem Salame,
  • Pierre Henri Bernard,
  • Claire Francoz,
  • Francois Durand,
  • Sébastien Dharancy,
  • Marie-lorraine Woehl,
  • Claire Vanlemmens,
  • Alexis Laurent,
  • Sylvie Radenne,
  • Jérôme Dumortier,
  • Armand Abergel,
  • Daniel Cherqui,
  • Louise Barbier,
  • Pauline Houssel-Debry,
  • Georges Philippe Pageaux,
  • Laurence Chiche,
  • Victor Deledinghen,
  • Jean Hardwigsen,
  • J. Gugenheim,
  • M. Altieri,
  • Marie Noelle Hilleret,
  • Thomas Decaens,
  • Daniel Cherqui,
  • Christophe Duvoux,
  • Federico Piñero,
  • Aline Chagas,
  • Paulo Costa,
  • Elaine Cristina de Ataide,
  • Emilio Quiñones,
  • Sergio Hoyos Duque,
  • Sebastián Marciano,
  • Margarita Anders,
  • Adriana Varón,
  • Alina Zerega,
  • Jaime Poniachik,
  • Alejandro Soza,
  • Martín Padilla Machaca,
  • Diego Arufe,
  • Josemaría Menéndez,
  • Rodrigo Zapata,
  • Mario Vilatoba,
  • Linda Muñoz,
  • Ricardo Chong Menéndez,
  • Martín Maraschio,
  • Luis G. Podestá,
  • M. Fauda,
  • A. Gonzalez Campaña,
  • Lucas McCormack,
  • Juan Mattera,
  • Adrian Gadano,
  • Ilka S.F. Fatima Boin,
  • Jose Huygens Parente García,
  • Flair Carrilho,
  • Marcelo Silva,
  • Andrea Notarpaolo,
  • Giulia Magini,
  • Lucia Miglioresi,
  • Martina Gambato,
  • Fabrizio Di Benedetto,
  • Cecilia D’Ambrosio,
  • Giuseppe Maria Ettorre,
  • Alessandro Vitale,
  • Patrizia Burra,
  • Stefano Fagiuoli,
  • Umberto Cillo,
  • Michele Colledan,
  • Domenico Pinelli,
  • Paolo Magistri,
  • Giovanni Vennarecci,
  • Marco Colasanti,
  • Valerio Giannelli,
  • Adriano Pellicelli,
  • Cizia Baccaro,
  • Helena Degroote,
  • Hans Van Vlierberghe,
  • Callebout Eduard,
  • Iesari Samuele,
  • Dekervel Jeroen,
  • Schreiber Jonas,
  • Pirenne Jacques,
  • Verslype Chris,
  • Ysebaert Dirk,
  • Michielsen Peter,
  • Lucidi Valerio,
  • Moreno Christophe,
  • Detry Olivier,
  • Delwaide Jean,
  • Troisi Roberto,
  • Lerut Jan Paul

Journal volume & issue
Vol. 3, no. 5
p. 100331

Abstract

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Background & Aims: Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and ‘all-comers’. Methods: This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000–2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs. Results: From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8–55.8) and 38.2% (CI 25.4–52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p <0.0001]) and not significantly higher for the UCSF-DS group (SHR 1.60 [p = 0.32]), compared with patients remaining within Milan. The all-comers presented more frequent features of aggressive HCC and higher tumour burden at explant. Among the UCSF-DS group, an AFP value of ≤20 ng/ml at listing was associated with lower recurrence (SHR 2.01 [p = 0.006]) and better survival. However, recurrence was still significantly high irrespective of AFP ≤20 ng/ml in all-comers. Conclusions: Patients within the UCSF-DS protocol at listing have similar post-transplant outcomes compared with those within Milan when successfully downstaged. Meanwhile, all-comers have a higher recurrence and inferior survival irrespective of response to LRT. Additionally, in the UCSF-DS group, an ALP of ≤20 ng/ml might be a novel tool to optimise selection of candidates for LT. Clinical trial number: This study was registered as part of an open public registry (NCT03775863). Lay summary: Patients with more extended HCC (within the UCSF-DS protocol) successfully downstaged to the conventional Milan criteria do not have a higher recurrence rate after LT compared with the group remaining in the Milan criteria from listing to transplantation. Moreover, in the UCSF-DS patient group, an ALP value equal to or below 20 ng/ml at listing might be a novel tool to further optimise selection of candidates for LT.

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