Turgeon MK, Shah SA, Delman AM, Tran BV, Agopian VG, Wedd JP, Magliocca JF, Kim A, Cameron A, Olyaei A, Orloff SL, Anderson MP, Kubal CA, Cannon RM, Locke JE, Simpson MA, Akoad ME, Wongjirad CP, Emamaullee J, Moro A, Aucejo F, Feizpour CA, Vagefi PA, Nguyen MH, Esquivel CO, Dhanireddy K, Subramanian V, Chavarriaga A, Kazimi MM, Anderson MS, Sonnenday CJ, Kim SC, Foley DP, Abdouljoud M, Salgia RJ, Moris D, Sudan DL, Ganesh SR, Humar A, Doyle M, Chapman WC, and Maithel SK. Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation. Ann Surg 2021; 274(4):613-620.
Annals of surgery
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.
Medical Subject Headings
Aged; Antiviral Agents; Benzimidazoles; Carbamates; Carcinoma, Hepatocellular; Drug Administration Schedule; Drug Combinations; Female; Fluorenes; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Pyrrolidines; Quinoxalines; Retrospective Studies; Sofosbuvir; Sulfonamides; Sustained Virologic Response