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Survival Benefit of Liver Transplantation for Hepatocellular Carcinoma

Kanneganti, Mounika BA*,1; Mahmud, Nadim MD MS MPH*,2; Kaplan, David E. MD MSc2,3; Taddei, Tamar H. MD4,5; Goldberg, David S. MD MSCE2,6

doi: 10.1097/TP.0000000000002816
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Background: In the US, nearly 30% of liver transplants (LT) are performed for hepatocellular carcinoma (HCC). Although overall long-term survival is highest with LT, there are limited data on the incremental survival benefit of LT versus other curative options (resection or ablation) due to shunting of patients towards LT.

Methods: We performed a retrospective cohort study of patients aged 50-69 with cirrhosis and HCC in the Veterans Health Administration (population enriched with three curative treatments) from 2008-2016. The cohort was restricted to patients who received LT, resection, or ablation and a calculated model for end-stage liver disease (MELD) score <15 at HCC diagnosis.

Results: Among 2,129 veterans in the analytic cohort, 658 (26.7%) received LT, 244 (11.5%) underwent resection, and 1,317 (61.59%) received ablation. In multivariable models, patients who underwent resection (HR: 5.42, 95% CI: 4.15-7.08) or ablation (HR: 5.50, 95% CI: 4.51-6.71) had significantly increased hazards of death. However, in absolute terms, the incremental survival benefit of LT over resection or ablation was small, between 0.02-0.03 years at one year, 0.32-0.42 years at three years, and 1.04-1.24 years at five years follow-up. These results were consistent in sensitivity analyses accounting for possible immortal time bias, as well as a cohort restricted to early/intermediate stage HCC.

Conclusion: Although LT is associated with significantly increased survival compared to resection and ablation, the absolute incremental survival benefit is small over a 5-year time horizon. Optimal selection of patients for LT is critical for maximizing utilization of a scarce resource.

1.Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

2.Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

3.Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

4.Division of Digestive Diseases, Yale University School of Medicine, New Haven, CT

5.VA Connecticut Healthcare System, West Haven, CT

6.Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

* Co-first authors

Financial Support: This work was supported by unrestricted research funds from Bayer Healthcare Pharmaceuticals and the VA HIV, Hepatitis and Public Health Pathogens Programs in the Office of Public Health/Clinical Public Health. This funding source had no role in data acquisition, analysis or interpretation of data. Nadim Mahmud is supported by a National Institutes of Health T32 grant (2-T32-DK007740-21A1).

Conflicts of interest: The views expressed in this article are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs of the U.S. Government. This work was supported in part by Health Resources and Services Administration contract 234-2005-37011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors have no additional disclosures.

Corresponding Author: David Goldberg, MD, MSCE, Department of Medicine, University of Pennsylvania, 423 Guardian Drive, 730 Blockley Hall, Philadelphia, PA 19104-6021, E-mail: david.goldberg@uphs.upenn.edu, Tel: +1-215-746-8598

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