Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients with Hepatocellular Carcinoma Presenting Beyond Milan Criteria. Hepatology (Baltimore, Md.) Kardashian, A. n., Florman, S. S., Haydel, B. n., Ruiz, R. M., Klintmalm, G. B., Lee, D. D., Taner, C. B., Aucejo, F. n., Tevar, A. D., Humar, A. n., Verna, E. C., Halazun, K. J., Chapman, W. C., Vachharajani, N. n., Hoteit, M. n., Levine, M. H., Nguyen, M. H., Melcher, M. L., Langnas, A. N., Carney, C. A., Mobley, C. n., Ghobrial, M. n., Amundsen, B. n., Markmann, J. F., Sudan, D. L., Jones, C. M., Berumen, J. n., Hemming, A. W., Hong, J. C., Kim, J. n., Zimmerman, M. A., Nydam, T. L., Rana, A. n., Kueht, M. L., Fishbein, T. M., Markovic, D. n., Busuttil, R. W., Agopian, V. G. 2020


The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are downstaged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of downstaging, and the impact of LRT in beyond-MC HCC patients from the US Multicenter HCC Transplant Consortium (20 centers, 2002-2013). Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n=3,570) and beyond MC (n=789) who were downstaged (DS, n=465), treated with LRT and not downstaged (LRT-NoDS, n=242), or untreated (NoLRT-NoDS, n=82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared to DS (64.3% and 59.5%), and lowest in NoDS (n=324; 60.2% and 53.8%; overall P<0.001). DS patients had superior RFS (60% vs 54%,P=0.043) and lower 5-year HCC-R (18% vs 32%,P<0.001) compared to NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/< 5cm and 39.1% in NoDS/>5cm,P<0.001). Multivariate predictors of downstaging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared to NoLRT-NoDS (34.1% vs 26.1%,P<0.001), even after controlling for clinicopathologic variables (HR=2.33,P<0.001) and inverse probability of treatment weighted propensity matching (HR=1.82,P<0.001). Conclusion In LT recipients with HCC presenting beyond MC, successful downstaging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden, and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared to NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.

View details for DOI 10.1002/hep.31210

View details for PubMedID 32124453