학술논문
R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation
Document Type
article
Author
Charlotte Costentin; Federico Piñero; Helena Degroote; Andrea Notarpaolo; Ilka F. Boin; Karim Boudjema; Cinzia Baccaro; Luis G. Podestá; Philippe Bachellier; Giuseppe Maria Ettorre; Jaime Poniachik; Fabrice Muscari; Fabrizio Dibenedetto; Sergio Hoyos Duque; Ephrem Salame; Umberto Cillo; Sebastian Marciano; Claire Vanlemmens; Stefano Fagiuoli; Patrizia Burra; Hans Van Vlierberghe; Daniel Cherqui; Quirino Lai; Marcelo Silva; Fernando Rubinstein; Christophe Duvoux; Filomena Conti; Olivier Scatton; Pierre Henri Bernard; Claire Francoz; Francois Durand; Sébastien Dharancy; Marie-lorraine Woehl; Alexis Laurent; Sylvie Radenne; Jérôme Dumortier; Armand Abergel; Louise Barbier; Pauline Houssel-Debry; Georges Philippe Pageaux; Laurence Chiche; Victor Deledinghen; Jean Hardwigsen; J. Gugenheim; M. Altieri; Marie Noelle Hilleret; Thomas Decaens; Aline Chagas; Paulo Costa; Elaine Cristina de Ataide; Emilio Quiñones; Sebastián Marciano; Margarita Anders; Adriana Varón; Alina Zerega; Alejandro Soza; Martín Padilla Machaca; Diego Arufe; Josemaría Menéndez; Rodrigo Zapata; Mario Vilatoba; Linda Muñoz; Ricardo Chong Menéndez; Martín Maraschio; Lucas McCormack; Juan Mattera; Adrian Gadano; Ilka S.F. Fatima Boin; Jose Huygens Parente García; Flair Carrilho; Giulia Magini; Lucia Miglioresi; Martina Gambato; Fabrizio Di Benedetto; Cecilia D’Ambrosio; Alessandro Vitale; Michele Colledan; Domenico Pinelli; Paolo Magistri; Giovanni Vennarecci; Marco Colasanti; Valerio Giannelli; Adriano Pellicelli; Cizia Baccaro; 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
Source
JHEP Reports, Vol 4, Iss 5, Pp 100445- (2022)
Subject
Language
English
ISSN
2589-5559
Abstract
Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.