Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation

Michael K. Turgeon, Shimul A. Shah, Aaron M. Delman, Benjamin V. Tran, Vatche G. Agopian, Joel P. Wedd, Joseph F. Magliocca, Ahyoung Kim, Andrew Cameron, Ali Olyaei, Susan L. Orloff, Matthew P. Anderson, Chandrashekhar A. Kubal, Robert M. Cannon, Jayme E. Locke, Mary A. Simpson, Mohamed E. Akoad, Chelsey P. Wongjirad, Juliet Emamaullee, Amika MoroFederico Aucejo, Cyrus A. Feizpour, Parsia A. Vagefi, Mindie H. Nguyen, Carlos O. Esquivel, Kiran Dhanireddy, Vijay Subramanian, Alejandro Chavarriaga, Marwan M. Kazimi, Maia S. Anderson, Christopher J. Sonnenday, Steven C. Kim, David P. Foley, Marwan Abdouljoud, Reena J. Salgia, Dimitrios Moris, Debra L. Sudan, Swaytha R. Ganesh, Abhinav Humar, Majella Doyle, William C. Chapman, Shishir K. Maithel

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Abstract

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Original languageEnglish
Pages (from-to)613-620
Number of pages8
JournalAnnals of surgery
Volume274
Issue number4
DOIs
StatePublished - Oct 1 2021

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