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R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation

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dc.contributor.authorCostentin, Charlotte
dc.contributor.authorPiñero, Federico
dc.contributor.authorDegroote, Helena
dc.contributor.authorNotarpaolo, Andrea
dc.contributor.authorBoin, Ilka
dc.contributor.authorBoudjema, Karim
dc.contributor.authorBaccaro, Cinzia
dc.contributor.authorPodestá, Luis
dc.contributor.authorBachellier, Philippe
dc.contributor.authorGiuseppe , Maria
dc.contributor.authorPoniachik, Jaime
dc.contributor.authorMuscari, Fabrice
dc.contributor.authorDibenedetto, Fabrizio
dc.contributor.authorHoyos, Sergio
dc.contributor.authorSalame, Ephrem
dc.contributor.authorCillo, Umberto
dc.contributor.authorMarciano, Sebastian
dc.contributor.authorVanlemmens, Claire
dc.contributor.authorFagiuoli, Stefano
dc.contributor.authorBurra, Patrizia
dc.contributor.authorVan Vlierberghe, Hans
dc.contributor.authorCherqui, Daniel
dc.contributor.authorLai, Quirino
dc.contributor.authorSilva, Marcelo
dc.contributor.authorRubinstein, Fernando
dc.contributor.authorDuvoux, Christophe
dc.date.accessioned2023-04-27T13:36:13Z
dc.date.available2023-04-27T13:36:13Z
dc.date.issued2022
dc.description.abstractBackground & 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.
dc.description.versionVersión Publicada
dc.identifier.citationCostentin C, Piñero F, Degroote H, Notarpaolo A, Boin IF, Boudjema K, Baccaro C, Podestá LG, Bachellier P, Ettorre GM, Poniachik J, Muscari F, Dibenedetto F, Duque SH, Salame E, Cillo U, Marciano S, Vanlemmens C, Fagiuoli S, Burra P, Van Vlierberghe H, Cherqui D, Lai Q, Silva M, Rubinstein F, Duvoux C; French-Italian-Belgium and Latin American collaborative group for HCC and liver transplantation. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation. JHEP Rep. 2022 Feb 2;4(5):100445. doi: 10.1016/j.jhepr.2022.100445
dc.identifier.doihttps://doi.org/10.1016/j.jhepr.2022.100445
dc.identifier.urihttps://repositorio.udd.cl/handle/11447/7412
dc.language.isoen
dc.subjectAFP
dc.subjectAlpha-foetoprotein
dc.subjectExplants pathology
dc.subjectHBV
dc.subjectHepatitis B virus
dc.subjectHCC
dc.subjectHepatocellular carcinoma
dc.subjectHCV
dc.subjectHepatitis C virus
dc.subjectLT
dc.subjectLiver transplantation
dc.subjectLiver cancer
dc.subjectLiver transplantation
dc.subjectMVI
dc.subjectMicrovascular invasion
dc.subjectPrediction
dc.subjectR3
dc.subjectRecurrence risk reassessment
dc.subjectRETREAT
dc.subjectRisk Estimation of Tumour Recurrence After Transplant
dc.subjectRecurrence
dc.subjectSHR
dc.subjectSub-distribution of hazard ratio
dc.subjectTC
dc.subjectTest cohort
dc.subjectTTR
dc.subjectTime to recurrence
dc.subjectVC
dc.subjectValidation cohort.
dc.titleR3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation
dc.typeArticle
dcterms.accessRightsAcceso abierto
dcterms.sourceJHEP reports : innovation in hepatology
dspace.entity.typePublication

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