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Optimal Timing Of Administration Of Direct-Acting Antivirals For Patients With Hepatitis C-Associated Hepatocellular Carcinoma Undergoing Liver Transplantation
*Michael K. Turgeon1, Shimul A. Shah2, *Aaron A. Delman2, *Benjamin V. Tran3, *Vatche G. Agopian3, *Joel P. Wedd1, *Joseph F. Magliocca1, *Matthew P. Anderson4, *Chandrashekhar A. Kubal4, *Robert M. Cannon5, Jayme E. Locke5, *Mary A. Simpson6, *Mohamed E. Akoad6, *Chelsey P. Wongjirad7, *Juliet Emamaullee7, *Amika Moro8, *Federico Aucejo8, *Cyrus A. Feizpour9, *Parsia A. Vagefi9, *Mindie H. Nguyen10, Carlos O. Esquivel10, *Kiran Dhanireddy11, *Vijay Subramanian11, *Maia S. Anderson12, *Christopher J. Sonneday12, *Dimitrios Moris13, Debra L. Sudan13, *Marwan Abdouljoud14, *Reena J. Salgia14, *Swaytha R. Ganesh15, Abhinav Humar15, Majella Doyle16, William C. Chapman16, Shishir K. Maithel1
1Emory University, Atlanta, GA;2University of Cincinnati College of Medicine, Cincinnati, OH;3David Geffen School of Medicine at UCLA, Los Angeles, CA;4Indiana University Health, Indianapolis, IN;5University of Alabama, Birmingham, AL;6Lahey Hospital and Medical Center, Boston, MA;7Keck School of Medicine of University of Southern California, Los Angeles, CA;8Cleveland Clinic Foundation, Cleveland, OH;9UT Southwestern Medical Center, Dallas, TX;10Stanford University, Stanford, CA;11Tampa General Hospital, Tampa, FL;12University of Michigan, Ann Arbor, MI;13Duke University School of Medicine, Durham, NC;14Henry Ford Health System, Detroit, MI;15University of Pittsburgh Medical Center, Pittsburgh, PA;16Washington University School of Medicine at St. Louis, St. Louis, MO

OBJECTIVE(S): In patients with hepatitis C (HCV) associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT), the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains unknown.
METHODS: The United States HCC-HCV Liver Transplantation Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and completed DAA therapy at 16 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS).
RESULTS: Of 675 patients, 588 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 70%, p<0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 92%, 92%, and 84%, and 5-year RFS of 92%, 97%, and 87%, respectively. On subgroup analysis of 349 HCV treatment-na´ve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (92% vs 69%, p<0.01) (Figure-1A). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 93%, 91%, and 79% (p=0.02) and 5-year RFS of 93%, 100%, and 86% (Figure-1B).
CONCLUSIONS: The optimal timing of DAA therapy appears to be 0-3 months after liver transplantation for HCV-associated HCC, given increased rates of SVR and a trend towards improved RFS. Delayed administration after transplant should be avoided, if possible. A randomized prospective trial is warranted to validate these results.


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