Development and validation of a REcurrent Liver cAncer Prediction ScorE (RELAPSE) following liver transplantation in patients with hepatocellular carcinoma: analysis of the us multicenter hcc transplant consortium. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Tran, B. V., Moris, D., Markovic, D., Zaribafzadeh, H., Henao, R., Lai, Q., Florman, S. S., Tabrizian, P., Haydel, B., Ruiz, R. M., Klintmalm, G. B., Lee, D. D., Taner, C. B., Hoteit, M., Levine, M. H., Cillo, U., Vitale, A., Verna, E. C., Halazun, K. J., Tevar, A. D., Humar, A., Chapman, W. C., Vachharajani, N., Aucejo, F., Lerut, J., Ciccarelli, O., Nguyen, M. H., Melcher, M. L., Viveiros, A., Schaefer, B., Hoppe-Lotichius, M., Mittler, J., Nydam, T. L., Markmann, J. F., Rossi, M., Mobley, C., Ghobrial, M., Langnas, A. N., Carney, C. A., Berumen, J., Schnickel, G. T., Sudan, D. L., Hong, J. C., Rana, A., Jones, C. M., Fishbein, T. M., Busuttil, R. W., Barbas, A. S., Agopian, V. G. 2023


Hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need.Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the United States Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (MLA; Random Survival Forest [RSF] and Classification and Regression Tree (CART) models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant (EurHeCaLT) study group.Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria (MC), 16.1% were initially beyond MC with 9.4% downstaged prior to LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1-, 3-, and 5-years was 89.7%, 78.6%, 69.8% and 86.8%, 74.9%, 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 mo) and non-HCC mortality of 20.8%. A multivariable model identified maximum AFP (HR = 1.35 per-log SD, 95%-CI:1.22-1.50,p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95%-CI:1.04-1.28,p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95%-CI 1.35-1.73,p < 0.001), microvascular (HR = 2.37, 95%-CI:1.87-2.99,p < 0.001) and macrovascular (HR = 3.38, 95%-CI:2.41-4.75,p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95%-CI:1.29-2.37,p < 0.001; poor HR = 2.62, 95%-CI:1.54-3.32,p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). MLAs incorporating additional covariates improved prediction of recurrence (RSF C-statistic = 0.81). Despite significant differences in EurHeCaLT recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2 and 5-year recurrence risk discrimination (AUC 0.77 and 0.75, respectively).We develop and externally validate a RELAPSE score which accurately discriminates post-LT HCC recurrence risk, and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.

View details for DOI 10.1097/LVT.0000000000000145

View details for PubMedID 37029083